Hippo pathway bioluminescent biosensor

ABSTRACT

Bioluminescent biosensors useful for monitoring and/or quantifying, in vitro or in vivo, activity of the Hippo signaling pathway. The biosensors monitor LATS kinase activity or YAP-TEAD interaction. The biosensors may be used in methods for monitoring and/or quantifying in real-time, in vitro or in vivo, activity of the Hippo signaling pathway, wherein the activity may be LATS kinase activity and/or YAP-TEAD interaction. The biosensors may be provided in kits for monitoring and/or quantifying in real-time, in vitro or in vivo, activity of the Hippo signaling pathway, wherein the activity may be LATS kinase activity and/or YAP-TEAD interaction.

REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

The contents of the electronic sequence listing (16177691sequencelistingST25-2.txt; size: 180 kB; date of creation: Aug. 19, 2022) is herein incorporated by reference in its entirety.

RELATED APPLICATION

This application claims the benefit of the filing date of Application No. 62/580,186, filed Nov. 1, 2017, the contents of which are incorporated herein by reference in their entirety.

FIELD

This invention relates to bioluminescent biosensors for non-invasively monitoring and/or quantifying in real-time, in vitro or in vivo, activity of the Hippo signaling pathway.

BACKGROUND

Detailed understanding of biochemical pathways will elucidate signaling mechanisms in physiological and pathological processes, yielding insight into approaches for controlling, treating, and preventing many diseases. The ability to gain such insight is severely limited by the complexity of such pathways and the difficulty in monitoring the activity of key components once identified.

The Hippo pathway is a signaling cascade that plays important roles in development (e.g., organ size control, 3D body shape, and early embryo development), cancer (tumorigenesis, metastasis, drug resistance, and immune evasion), regeneration medicine (stem cell renewal and differentiation and tissue homeostasis/regeneration), heart development and disease (cardiomyocyte proliferation and heart infarction/cardiac injury) and in the neuronal system (neural fate and dendrite tiling)¹⁻⁹. Dysregulation of the Hippo pathway is frequently observed in human cancers. When Hippo signaling is activated by upstream regulators, MST1/2 serine/threonine (S/T) kinases (mammalian homologs of Drosophila Hippo) phosphorylate/activate LATS1/2 kinases which subsequently phosphorylate/inactivate their downstream effectors, transcriptional co-activator Yes-associated protein (YAP) and its paralog transcriptional co-activator with PDZ-binding motif (TAZ). S127-phosphorylated YAP (YAP-pS127) or S89-phosphorylated TAZ (TAZ-pS89) bind to cytoplasmic protein 14-3-3 and are prevented from binding to transcription factor TEAD to trans-activate downstream gene targets in the nucleus (e.g., CTGF, CYR61, FGF1, etc.)¹⁰⁻¹⁴. Although a few regulatory factors of the Hippo pathway have been uncovered (actin dynamics, cell matrix stiffness, cell-cell contact, and lysophosphatidic acid (LPA)^(3, 6), comprehensive regulator screens have been technically limited. An absence of available tools precludes measuring the dynamics and activity of the Hippo pathway core components in a quantitative, high-throughput and non-invasive manner.

SUMMARY

One aspect of the invention relates to a luminescent biosensor, comprising: one or more fragments of firefly or NanoBiT luciferase or a functional equivalent thereof; at least one fragment of human YAP or a functional equivalent thereof; and at least one vector.

In one embodiment, the biosensor comprises: a first construct comprising an N-terminal luciferase fragment (Nluc) or a functional equivalent thereof fused to the at least one YAP fragment; a second construct comprising a C-terminal luciferase fragment (Cluc) or a functional equivalent thereof fused to human cytoplasmic 14-3-3 protein or a functional equivalent thereof; wherein the first construct and the second construct are on separate vectors; wherein LATS-dependent phosphorylation of the at least one YAP fragment leads to binding with the human cytoplasmic 14-3-3 protein, which results in binding of Nluc and Cluc to produce luminescence.

In one embodiment, the biosensor comprises Nluc luciferase amino acids 1-416 of SEQ ID NO:6 or a functional equivalent thereof; Cluc luciferase amino acids 394-550 of SEQ ID NO:6 or a functional equivalent thereof; and YAP fragment including 15 amino acids (residues 120-134; SEQ ID NO:7) or a functional equivalent thereof.

In one embodiment, the biosensor comprises a single construct including: an N-terminal luciferase fragment (Nluc) or a functional equivalent thereof fused to the at least one YAP fragment; and a C-terminal luciferase fragment (Cluc) or a functional equivalent thereof fused to human cytoplasmic 14-3-3 protein; wherein LATS-dependent phosphorylation of the at least one YAP fragment leads to a conformational change and binding of Nluc and Cluc to produce luminescence.

In one embodiment, the biosensor comprises Nluc luciferase amino acids 1-416 of SEQ ID NO:6 or a functional equivalent thereof; Cluc luciferase amino acids 394-550 of SEQ ID NO:6 or a functional equivalent thereof; and YAP fragment including 15 amino acids (residues 120-134; SEQ ID NO:7) or a functional equivalent thereof.

In one embodiment, the biosensor comprises a single construct including a luciferase engineered at the C-terminal fused to the one or more YAP fragment; wherein LATS-dependent phosphorylation of the one or more YAP fragment modulates luciferase activity to increase luminescence. In one embodiment, the luciferase is engineered at the C-terminal consisting of amino acids 1-544 (SEQ ID NO:6) or a functional equivalent thereof.

In one embodiment, the biosensor comprises a first construct comprising a LgBiT luciferase fragment or a functional equivalent thereof fused to the at least one YAP fragment or a functional equivalent thereof a second construct comprising a SmBiT luciferase fragment or a functional equivalent thereof fused to human cytoplasmic 14-3-3 protein or a functional equivalent thereof; wherein the first construct and the second construct are on separate vectors; wherein binding of the at least one YAP fragment with the human cytoplasmic 14-3-3 protein and leads to binding of LgBiT and SmBiT to produce luminescence. In one embodiment, the biosensor comprises YAP fragment including 15 amino acids (residues 120-134; SEQ ID NO:7) or a functional equivalent thereof.

In one embodiment, the biosensor comprises: a first construct comprising a LgBiT luciferase fragment or a functional equivalent thereof fused to the at least one YAP fragment or a functional equivalent thereof; a second construct comprising a SmBiT luciferase fragment or a functional equivalent thereof fused to a TEAD fragment or a functional equivalent thereof, or a first construct comprising a LgBiT luciferase fragment or a functional equivalent thereof fused to a TEAD fragment or a functional equivalent thereof; a second construct comprising a SmBiT luciferase fragment or a functional equivalent thereof fused to the at least one YAP fragment or a functional equivalent thereof; wherein the first construct and the second construct are on separate vectors; wherein interaction of the at least one YAP fragment with the TEAD fragment leads to binding of LgBiT and SmBiT to produce luminescence.

In one embodiment, the biosensor comprises: YAP fragment comprising amino acids 50-171 of SEQ ID NO:2 or a functional equivalent thereof; and TAED fragment comprising amino acids 194-411 of SEQ ID NO:50 or a functional equivalent thereof.

Another aspect of the invention relates to a method, comprising: non-invasively monitoring and/or quantifying in real-time, in vitro or in vivo, activity of the Hippo signaling pathway, comprising transfecting a cell with a luminescent biosensor as described herein, and detecting luminescence; wherein an intensity of the luminescence is indicative of amount of activity of the Hippo signaling pathway.

Another aspect of the invention relates to a method for monitoring and/or quantifying activity of the Hippo signaling pathway, comprising: treating a cell with a luminescent biosensor as described herein; and detecting luminescence of the treated cell; wherein an intensity of the luminescence is indicative of amount of activity of the Hippo signaling pathway. In one embodiment, an intensity of the luminescence is indicative of amount of LATS kinase activity in the Hippo signaling pathway. In one embodiment, an intensity of the luminescence is indicative of amount of YAP-TEAD interaction in the Hippo signaling pathway. In one embodiment, treating a cell comprises transfecting a cell with the luminescent biosensor. In one embodiment, treating a cell comprises lysing the cell and combining a cell lysate with the luminescent biosensor.

In one embodiment, the method comprises: non-invasively monitoring and/or quantifying in real-time, in vitro or in vivo, activity of LATS kinase, comprising transfecting the cell with a luminescent biosensor as described herein, and detecting luminescence; wherein an intensity of the luminescence is indicative of amount of LATS kinase activity in the Hippo signaling pathway.

In one embodiment, the method comprises: non-invasively monitoring and/or quantifying in real-time, in vitro or in vivo, YAP-TEAD interaction, comprising transfecting the cell with a luminescent biosensor as described herein, and detecting luminescence; wherein an intensity of the luminescence is indicative of amount of YAP-TEAD interaction in the Hippo signaling pathway.

Another aspect of the invention relates to a method, comprising: monitoring and/or quantifying activity of one or more proteins of the Hippo signaling pathway, comprising combining the one or more proteins with a luminescent biosensor as described herein and at least one substance, and detecting luminescence of the luminescent biosensor; wherein an intensity of the luminescence is indicative of effect of the at least one substance on activity of the one or more proteins of the Hippo signaling pathway.

In various embodiments of the above method, the at least one substance is selected from a chemical compound such as a small molecule inhibitor (e.g., molecular weight below about 500 Daltons), a large molecule inhibitor (e.g., molecular weight above about 500 Daltons), a biological agent (e.g., antibody), protein, polypeptide, peptide, DNA aptamer, microRNA, interfering RNA (shRNA, siRNA), a sugar, lipid, glycoprotein, and glycolipid.

Another aspect of the invention relates to a method for monitoring and/or quantifying activity of the Hippo signaling pathway in a biological sample obtained from a subject, comprising: treating cells of the biological sample with at least one reagent comprising the a luminescent biosensor as described herein; and detecting luminescence of the treated biological sample; wherein an intensity of the luminescence is indicative of amount of activity of the Hippo signaling pathway. In one embodiment, an intensity of the luminescence is indicative of amount of LATS kinase activity in the Hippo signaling pathway. In one embodiment, an intensity of the luminescence is indicative of amount of YAP-TEAD interaction in the Hippo signaling pathway. In various embodiments, the biological sample comprises at least one of tissue and blood. In one embodiment, the biological sample comprises blood. In one embodiment, an intensity of the luminescence is indicative of the cells being cancer cells.

Another aspect of the invention relates to a kit, comprising: a luminescent biosensor as described herein; at least one reagent; and, optionally, instructions for using the kit.

BRIEF DESCRIPTION OF THE DRAWINGS

For a greater understanding of the invention, and to show more clearly how it may be carried into effect, embodiments will be described, by way of example, with reference to the accompanying drawings, wherein:

FIG. 1A is a schematic diagram of YAP1 protein structure (SEQ ID NO:2) showing LATS phosphorylation site (S127) and the surrounding 15 amino acid sequence (YAP15; SEQ ID NO:7).

FIG. 1B is a western blot for GST pulldown assays showing results confirming that YAP15 is sufficient for interaction with cytoplasmic protein 14-3-3 in vitro.

FIG. 2A shows schematic diagrams of domain structures of a LATS intermolecular biosensor, referred to as Nluc-YAP15 (upper; SEQ ID NOs:6, 7) and 14-3-3-Cluc (lower; SEQ ID NOs:4, 6), according to an embodiment of the invention.

FIG. 2B is a schematic diagram showing the mechanism by which a LATS intermolecular biosensor determines LATS kinase activity.

FIG. 2C shows experimental results validating LATS intermolecular biosensor activity, where biosensor activity or NLuc-YAP15-S127 phosphorylation status were determined in HEK293 cells 48 hours after transfection by luciferase assay or western blot, respectively. Data are presented as mean±SD, n=3.

FIG. 2D shows experimental results confirming that a LATS intermolecular biosensor responds specifically to LATS kinase activity, by mutation of the LATS kinase consensus motif (HXRXXS/T; H, histidine; R, arginine; X, any amino acid; S, serine; T, threonine; SEQ ID NOs:71, 72) in Nluc-YAP15 (SEQ ID NOs:7, 8). Data are presented as mean±SD, n=3.

FIG. 2E shows experimental results confirming that LATS intermolecular biosensor activity is reduced by MST or LATS knockout. Data are presented as mean±SD, n=3.

FIG. 2F shows experimental results confirming that LATS intermolecular biosensor can be stably expressed to detect LATS kinase activity, wherein biosensor activity and phosphorylation status were monitored in a HEK293A cell line with doxycycline (Dox)-inducible LATS2 overexpression and stable LATS biosensor (LATS-BS) expression, and biosensor activity and phosphorylation status of endogenous YAP (YAP-pS127) and Nluc-YA15P-S127 (Nluc-YAP15-pS127) were determined at the indicated times by luciferase assay and western blot, respectively. Data are presented as mean±SD, n=3.

FIG. 3A is a schematic diagram showing the domain structure of a LATS intramolecular biosensor based on SEQ ID NOs:6, 7, 73, according to one embodiment.

FIG. 3B is a schematic diagram showing the mechanism by which a LATS intramolecular biosensor determines LATS kinase activity.

FIG. 3C is a bar chart showing results of a validation study of an intramolecular LATS biosensor according to the embodiment of FIG. 3A.

FIG. 4A is a schematic diagram showing the domain structure of an engineered LATS biosensor based on SEQ ID NOs:6, 7, according to one embodiment.

FIG. 4B is a schematic diagram showing the mechanism by which an engineered LATS biosensor determines LATS kinase activity.

FIG. 4C is a bar chart showing results of a validation study of an engineered LATS biosensor according to the embodiment of FIG. 4A.

FIGS. 5A-5D show diagrams of multiple cloning sites of vectors (pBiT1.1-N [TK/LgBiT; 5A]; pBiT2.1-C [TK/SmBiT; 5B]; pET16b (5C)) and domain structures of constructs (5D) used to make NanoBiT (NanoLuc) biosensors based on Nluc and CLuc (SEQ ID NO:6), YAP15 (SEQ ID NO:7), LgBiT (SEQ ID NO:52), SmBiT (SEQ ID NO:54), and 14-3-3 (SEQ ID NO:4), according to embodiments of the invention.

FIG. 6 is a schematic diagram showing an overview of a NanoBiT interaction system of a LATS NanoBiT biosensor according to an embodiment of the invention.

FIG. 7 shows a coomassie brilliant blue (CBB) stained SDS-PAGE of purified proteins for a LATS NanoBiT biosensor.

FIG. 8A shows results of a NanoBiT biosensor assay of overexpressed LgBiT-YAP15 WT and mutant (MUT) and 14-3-3-SmBiT in HEK293T cells as relative luminescence to YAP15MUT-14-3-3.

FIG. 8B shows results of a NanoBiT LATS biosensor assay for cancer cells.

FIG. 8C shows results of a NanoBiT LATS biosensor assay for blood.

FIG. 9 shows results of an in vitro NanoBiT biosensor assay using purified LgBiT-YAP15 (WT and mutant), 14-3-3-SmBiT, and LATS2 kinase; upper panel shows the result of the NanoBiT assay for YAP15WT or mutant at two different concentrations of biosensor (5 and 100 ng) as a ratio of luminescence signal at different time points; lower panel shows immunoblotting analysis and ponceau staining of the respective samples with 100 ng of biosensor.

FIG. 10 shows the results of a kinase assay with purified proteins; upper panel shows the NanoBiT LATS biosensor assay for YAP15 WT and mutant (100 ng) with and without lambda phosphatase after 30 min; the lower panels show the relative immunoblotting and Ponceau staining for the respective samples.

FIG. 11 shows diagrams of domain structures of eight constructs used to make a YAP-TEAD biosensor based on LgBiT (SEQ ID NO:52), SmBiT (SEQ ID NO:54), YAP50-171 (SEQ ID NO:2), and TEAD1-194-411 (SEQ ID NO:50), according to one embodiment.

FIG. 12 shows a schematic overview of a NanoBiT interaction system of a YAP-TEAD NanoBiT biosensor according to an embodiment of the invention.

FIG. 13 shows the results of an assay of overexpressed YAP50-171 of SEQ ID NO:2 and TEAD1-194-411 of SEQ ID NO:50 in HEK293T cells lysed with passive lysis buffer, for a biosensor with a combination of SmBiT-YAP50-171 (SEQ ID NO:2) and LgBiT-TEAD1-194-411 of SEQ ID NO:50 constructs.

FIG. 14 shows the results of an assay for analyzing LATS kinase activity under various stimuli regulating Hippo signaling by live cell luciferase imaging, using an intermolecular LATS-BS as described herein.

FIG. 15 is a photomicrograph showing the results of an experiment to determine subcellular LATS kinase activity using an intermolecular LATS-BS as described herein, obtained by bioluminescent microscopy.

FIG. 16 is a photograph showing LATS kinase activity in mice by in vivo luciferase imaging, using an intermolecular LATS-BS as described herein.

FIG. 17A is a schematic diagram showing a method for a screening assay, and FIG. 17B shows the results of a screening assay for identifying novel regulators of LATS using an intermolecular LATS-BS as described herein and a kinase inhibitor screen.

DETAILED DESCRIPTION OF EMBODIMENTS

In practicing the embodiments described herein, many conventional techniques in cell biology, molecular biology, protein biochemistry, immunology, and bacteriology are used. These techniques are well-known in the art and are provided in any number of available publications, such as Current Protocols in Molecular Biology, Vols. I-III, Ausubel, Ed. (1997); Sambrook et al., Molecular Cloning: A Laboratory Manual, Second Ed. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989). Unless specifically defined herein, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

One aspect of the invention relates to bioluminescence-based biosensor constructs that non-invasively monitor real-time in vitro and in vive activity of LATS kinase, the central player of the Hippo signaling pathway. A LATS biosensor (LATS-BS) as described herein quantifies LATS kinase activity by split luciferase assay, a bioluminescence-based technique that non-invasively monitors protein-protein interactions in vitro and in vive in real-time with accurate quantification, high sensitivity, and excellent reproducibility. Embodiments of the biosensor constructs include fragments of firefly (Photinus sp., e.g., Photinus pyralis) or NanoBiT (also referred to as NanoLuc) luciferase and human YAP1. Some embodiments include human cytoplasmic protein 14-3-3 or a fragment thereof.

Another aspect of the invention relates to a method for non-invasively monitoring real-time in vitro and in vivo activity of LATS kinase. In various embodiments, the method includes using a LATS biosensor as described herein to quantify LATS kinase activity. The embodiments provide a bioluminescence-based technique for monitoring LATS kinase activity with accurate quantification, high sensitivity, and excellent reproducibility (see Examples for details).

A third aspect of the invention relates to bioluminescent biosensor constructs and methods for non-invasively monitoring YAP-TEAD interaction, a critical step in regulation of downstream target by the Hippo pathway. Embodiments of the biosensor constructs include fragments of NanoBiT luciferase and fragments of human YAP1 and TEAD1, or functional equivalents thereof, and provide a bioluminescent-based technique for monitoring YAP and TEAD interactions both in vitro and in vivo with high sensitivity, stability, and reproducibility.

At least eight isoforms of YAP1 are known. SEQ ID NO:1 shows the full human YAP2L isoform mRNA (accession number: AB567720) and SEQ ID NO:2 shows the amino acid sequence. The fragments used in the embodiments described herein were obtained from the YAP2L isoform of YAP1 (SEQ ID NO:2). However, the fragments used in the embodiments described herein may be obtained from any of the isoforms, or may be functional equivalents thereof. In this disclosure, the terms “YAP1” and “YAP” are used interchangeably to refer to an isoform of YAP1. SEQ ID NO:3 shows the full human 14-3-3 protein theta mRNA (accession number: P27348) and SEQ ID NO:4 shows the amino acid sequence. SEQ ID NO:5 shows the full length firefly luciferase mRNA and SEQ ID NO:6 shows the luciferase protein.

Since LATS phosphorylates S127 on YAP1 and cytoplasmic protein 14-3-3 binds specifically to phosphorylated but not un-phosphorylated S127-YAP, embodiments were constructed for monitoring LATS kinase activity by measuring the pS127-YAP/14-3-3 interaction.

In various embodiments, a LATS-BS includes a minimal YAP1 fragment that interacts with 14-3-3 in a phosphorylation-dependent manner. The full length YAP1 protein was not used to avoid confounding signals by post-translational modifications of YAP1 by other upstream regulators. In one embodiment, the minimal YAP1 fragment includes 15 amino acids (YAP15) surrounding the 5127 LATS phosphorylation site (amino acids 120-134; SEQ ID NO:7; FIG. 1A). Functional equivalents may be used, such as other sizes of YAP1 fragments, such as, for example, longer (e.g., 16-20 amino acids) or shorter (e.g., 12-14 amino acids) surrounding the S127 (SEQ ID NO:2). Embodiments may include a YAP fragment with a HxRxxS motif (SEQ ID NO:71). Since H, R, and S residues but not other amino acids in the HxRxxS motif (SEQ ID NO:71) on the YAP fragment are essential for LATS biosensor function (see, e.g., FIG. 2D), variants of YAP fragments with changes of amino acids other than H/R/S may also be used. Larger fragments (e.g., 20-100 amino acids) may result in confounding signals.

Minimal YAP1 fragments were tested for interaction with 14-3-3 after phosphorylation by LATS2 kinase. Using in vitro GST-pulldown assays, it was found that like full-length YAP-GST, YAP15-GST could directly bind to 14-3-3 after LATS phosphorylation while a phosphorylation-mutant YAP15-S127A-GST (A, alanine) could not. FIG. 1B shows that YAP15 is sufficient for interaction with 14-3-3 in vitro. To collect the data, GST-tagged full length YAP (YAP-GST), YAP15 with wild type sequence (YAP15-S127-GST), or mutant YAP15 that cannot be phosphorylated by LATS (YAP15-S127A-GST) was purified from bacterial cells and 1 μg of GST fusion protein was incubated for 20 minutes at 30° C. with recombinant LATS kinase. 100 μg of cell lysate from human embryonic kidney cells (HEK293) transiently expressing 14-3-3-Flag was added and YAP or YAP15-S127 or YAP15-S127A/14-3-3 binding was assessed by GST pull-down with protein S-agarose beads, followed by western blot with anti-Flag (14-3-3-Flag) and anti-YAP-pS127 antibodies. The membrane was stained with Ponceau S to visualize the fusion proteins.

Since the TEAD family consists of four members, other TEADs (TEAD2-4) may also be used to replace TEAD1 to make biosensors similar to the YAP-TEAD1 biosensor. Throughout this disclosure, “TEAD1” and “TEAD” are used interchangeably to refer to any one of the TEAD family members.

In the following descriptions of various embodiments of the biosensor, references to sequences and sequence listings are made. Those of ordinary skill in the art will readily appreciate that the invention is not limited to the specific sequences described, as many variants are possible without departing from the invention. For example, substitutions, mutations, deletions, and/or additions of one or more nucleotides or amino acids may be made, or may occur, without substantial effect on functional properties of a biosensor. Such a functional equivalent may have, for example, 60%, or 70%, or 80%, or 90%, or more sequence identity with a sequence described herein. Such functional equivalents are intended to be included in the embodiments of the invention.

1. LATS Biosensor 1.1 Intermolecular Biosensor

The biosensor was made by overlapping PCR using firefly luciferase as a template. YAP15 and 14-3-3 were fused with N-terminal and C-terminal luciferase fragments (Nluc and Cluc), respectively, to create a LATS-B S. As shown in FIG. 2A, for Nluc-YAP15, firefly luciferase amino acids 1-416 (N-luciferase, Nluc) (SEQ ID NO: 6) were fused to the N-terminal of YAP15 (120-134; SEQ ID NO:7) separated by a glycine/alanine linker (GGAGG; SEQ ID NO:73); and for 14-3-3-Clue, luciferase amino acids 394-550 (C-luciferase, Cluc; SEQ ID NO:6) were fused to the C-terminal of 14-3-3 (SEQ ID NO: 4) separated by a glycine/serine linker (GGSGGGGSGG; SEQ ID NO:74). Biosensors were cloned into the BamHI/NotI sites of the pcDNA3.1/hygro (+) vector (SEQ ID NO:9, purchased from Invitrogen, Dublin, Ireland). Primers are shown in SEQ ID NOs:10-16. The full length sequences for Nluc-YAP15 and 14-3-3-Clue in pcDNA3.1/hygro (+) vector are given in SEQ ID NOs:57 and 58, respectively, wherein the underlined portions are the main constructs and the rest is the vector.

The mechanism of action for how the LATS-BS determines LATS kinase activity is shown in FIG. 2B. At baseline, there is no interaction between YAP15 and 14-3-3 so the LATS-BS shows minimal bioluminescence activity. However, LATS-dependent phosphorylation of YAP15-S127 leads to 14-3-3 binding, luciferase complementation, and high bioluminescence signal.

In a validation study, LATS-BS was transfected alone or together with LATS2 or/and MST2 into HEK293 cells and biosensor activity or NLuc-YAP15-S127 phosphorylation status were determined 48 hours after transfection by luciferase assay or western blot, respectively. As depicted in FIG. 2C, HEK293 cells transfected with LATS-BS alone had low luciferase activity and this was correlated with a low degree of Nluc-YAP15-S127 phosphorylation. Co-transfection of LATS-BS with MST2 was associated with increases in both Nluc-YAP-S127 phosphorylation and luciferase activity, and this effect was suppressed with lysophosphatidic acid (LPA), an inhibitor of the Hippo pathway. For lysophosphatidic acid (LPA) treatment, cells were stimulated with 10 μM LPA for 1 hour before collection (n=3). LATS-BS co-expression with both MST2 and LATS2 was correlated with further increases in Nluc-YAP15-S127 phosphorylation and luciferase activity. Collectively, these observations are consistent with a model where MST2 activates LATS2, which phosphorylates Nluc-YAP15-S127, leading to binding with Cluc-14-3-3 and reconstitution of active luciferase.

To further validate the biosensor construct model, conserved residues (H, histidine; R, arginine; S) within the LATS consensus phosphorylation motif (HxRxxS/T; x, any amino acid; SEQ ID NOs: 71, 72) on Nluc-YAP15-S127 were mutated to A (H122A, R124A, and S127A). Each individual mutation completely abolished Nluc-YAP15-S127 phosphorylation and LATS-BS luciferase activity, as shown in FIG. 2D. In addition, the basal LATS-BS signal was reduced by knockout of endogenous MST1/2 in HEK293A (50% reduction) or more dramatically by LATS1/2 knockout HO % reduction), as shown in FIG. 2E. LATS-BS was transfected into CRISPR-Cas9-generated LATS1/2 or MST1/2 knockout HEK293A and basal biosensor activity was determined 48 hours after transfection (n=3). Furthermore, inducible expression of LATS2 in HEK293A cells stably expressing LATS-BS showed that the levels of LATS2 are correlated with the level of endogenous YAP-pS127, Nluc-YAP15-pS127 as well as with LATS-BS activity, as shown in FIG. 2F. Biosensor activity and phosphorylation status were monitored in a HEK293A cell line with doxycycline (Dox)-inducible LATS2 overexpression and stable LATS-BS expression. Cells were treated with 1 μg/mL Dox for the indicated times and biosensor activity and phosphorylation status of endogenous YAP (YAP-pS127) and Nluc-YA15P-S127 (Nluc-YAP15-pS127) were determined by luciferase assay and western blot, respectively (n=3).

This LATS biosensor was also used to examine LATS kinase activity in living cells and mice and to perform a screening assay for regulators of LATS (see details in Examples).

1.2 Intramolecular Biosensor

An intramolecular biosensor was made by overlapping PCR using firefly luciferase as a template. In one embodiment, firefly luciferase amino acids 1-416 (N-luciferase, Nluc; SEQ ID NO:6) were fused to the N-terminal of YAP15 (120-134) (SEQ ID NO:7) separated by a glycine/alanine linker (GGAGG; SEQ ID NO:73). Within the same open reading frame, luciferase amino acids 394-550 (C-luciferase, Cluc; SEQ ID NO:6) were fused to the C-terminal of 14-3-3 separated by a glycine/alanine linker. For this biosensor, LATS phosphorylates YAP15-5127 to cause a conformational change in the intramolecular LATS-BS, leading to luciferase complementation and detectable biosensor activity. Primers are shown in SEQ ID NOs:10, 16, 17, and 18.

The domain structure is shown in FIG. 3A and the mechanism of action for how the LATS-BS determines LATS kinase activity is shown in FIG. 3B. At baseline, there is no interaction between YAP15 and 14-3-3 so the LATS-BS shows minimal bioluminescence activity. However, LATS-dependent phosphorylation of YAP15-S127 leads to 14-3-3 binding, luciferase complementation, and high bioluminescence signal.

To validate the intramolecular biosensor, the biosensor was transfected alone or together with LATS2 or/and MST2 into HEK293 cells and biosensor activity was determined 48 hours after transfection by luciferase assay. For LPA treatment, cells were stimulated with 10 μM LPA, an inhibitor of the Hippo pathway, for 1 hour before collection (n=3). Results are shown in FIG. 3C.

13 Engineered Biosensor

The biosensor was made by overlapping PCR using firefly luciferase as a template. In one embodiment, the C-terminal seven amino acids from firefly luciferase were removed to create Eng-luc (544 amino acids). This construct was fused to the N-terminal of YAP15 (amino acids 120-134; SEQ ID NO:7). This brings the luciferase site in close proximity to YAP15-5127 such that LATS-dependent phosphorylation of YAP-S127 modulates luciferase activity directly. Primers are shown in SEQ ID NOs:10 and 19.

The domain structure of the Eng-luc LATS biosensor according to one embodiment is shown in FIG. 4A and the mechanism of action for how the biosensor determines LATS kinase activity is shown in FIG. 4B.

For validation of the Eng-luc LATS-BS, the biosensor was transfected alone or together with LATS2 or/and MST2 into HEK293 cells and biosensor activity was determined 48 hours after transfection by luciferase assay. For LPA treatment, cells were stimulated with 10 μM LPA for 1 hour before collection (n=3). Results are shown in FIG. 4C.

1.4. NanoBiT Biosensor

For this biosensor YAP15 (aa 120-134; SEQ ID NO:7) and 14-3-3 full length (aa 1-245; SEQ ID NO:4) were used. As shown in FIG. 7-10 , a YAP15 mutant was used as a negative control in these experiments.

To clone YAP15 and 14-3-3 in NanoBiT (also referred to as NanoLuc) vectors (purchased from Promega Corporation, Madison, Wis., U.S.A.), primers with EcoR1 and Bglll restriction sites were used. For the LgBiT-YAP15 construct, primers shown in SEQ ID NOs:20-23 were used. For the 14-3-3-SmBiT construct, primers shown in SEQ ID NOs:24-25 were used.

In the case of YAP15WT (S127; SEQ ID NO:7) and mutant (A127; SEQ ID NO:8), primers with EcoR1 and Bglll flanking ends were annealed first and then they were ligated into digested pBiT 1.1 N (TK-LgBiT) vector (SEQ ID NO:26; purchased from Promega Corporation) with N-terminal LgBiT domain. FIG. 5A shows the multiple cloning site. For making the 14-3-3-SmBiT construct, in order to amplify 14-3-3 gene, standard PCR using the above mentioned primers was done by using 14-3-3 as a template. PCR product was digested using EcoR1 and Bglll restriction enzymes and was ligated into pBiT 2.1 C (TK-SmBiT; purchased from Promega Corporation) (SEQ ID NO:27) with SmBiT (11 amino acid) sequence at the C-terminus. FIG. 5B shows the multiple cloning site.

To make LgBiT-YAP15 (WT and mutant) and 14-3-3-SmBiT constructs for protein expression and purification in E. coli, the primers shown in SEQ ID NOs:28-30 were used for the LgBiT-YAP15 construct, and the primers shown in SEQ ID NOs:31-32 were used for the 14-3-3-SmBiT construct. For PCR, LgBiT-YAP15 and 14-3-3-SmBiT in NanoBiT vectors were used as template. pET16b vector (SEQ ID NO:33; purchased from Novagen (Millipore (Canada) Ltd., Etobicoke, Canada) was used for overexpression of LgBiT-YAP15 (WT and mutant) and 14-3-3-SmBiT as His-tagged proteins. FIG. 5C shows the multiple cloning site.

FIG. 5D shows a schematic representation of the LgBiT-YAP15 and 14-3-3-SmBiT constructs. SEQ ID NOs:59, 60, 61, and 62 give the full length sequences for LgBiT-YAP15 in pBiT 1.1 N vector, 14-3-3-LgBiT in pBiT2.1-C vector, LgBiT-YAP15 in pET16b vector, and SmBiT in pET16b vector, respectively, wherein the underlined portions are the main constructs and the rest is the vector.

FIG. 6 is a schematic diagram showing an overview of the NanoBiT interaction system. YAP15 and 14-3-3 are fused to LgBiT and SmBiT, respectively. Interaction of purified fusion proteins or overexpressed proteins in the cells leads to structural complementation of LgBiT with SmBiT that consequently generates a functional enzyme with bright luminescence.

For protein expression, the E. coli strain CodonPlus (DE3)-RIPL was transformed and used to purify the respective proteins. E. coli with the respective construct were grown until an OD600 value of 0.6-0.8 and then induced with 0.3 mM isopropyl-β-D-thiogalactopyranoside (IPTG) overnight at 20° C. Protein purification was carried out by incubating cells at 4° C. with DNase I (10 μg/ml) followed by cell lysis by sonication. Bacterial lysates were centrifuged to collect soluble fractions and His-tagged proteins were purified from the supernatant via Ni-affinity purification. After eluting and concentrating, proteins were subjected to dialysis against standard buffer containing 30 mM Tris-HCl, pH 7.5, 150 mM NaCl, 5 mM MgCl2, and 2 mM DTT. All purified proteins were analyzed by SDS-PAGE and stored at −80° C. FIG. 7 shows coomassie brilliant blue (CBB) stained SDS-PAGE of purified proteins for the biosensor.

NanoBiT Assay for YAP15-14-3-3 in Cells.

A NanoBiT assay was prepared for YAP15-14-3-3 in cells. HEK293T cells (3×10⁵) were transfected using Polyjet transfection reagent according to the manufacturer's instructions in 12-well plates by using 250 ng of each plasmid DNA per transfection. After 48 h the cells were lysed with passive lysis buffer and the NanoBiT assay of overexpressed LgBiT-YAP15 WT and mutant and 14-3-3-SmBiT was performed. Relative luminescence to YAP15MUT-14-3-3 was determined as shown in FIG. 8A.

NanoBiT Assay for YAP15-14-3-3 Using Cancer Cells.

Cancer cells (A549, H1299, and HEK293) were treated with okadaic acid for 1 h to activate LATS before lysing with passive lysis buffer. Then, 350 μg cell lysate was untreated or treated with calf intestine phosphatase (CIP) to inactivate the biosensor, followed by LATS pulldown and measurement of LATS kinase activity in vitro using purified LATS BS. As shown in FIG. 8B, the NanoBiT LATS-BS produced a strong signal for all three types of cancer cells.

NanoBiT Assay for YAP15-14-3-3 Using Blood.

Mononuclear cells were separated from fresh human blood and then lysed with passive lysis buffer. Then, 350 μg cell lysate was used to pull-down LATS kinase and measure its activity in vitro using purified NanoBiT LATS-BS. As shown in FIG. 8C, the NanoBiT LATS-BS produced a strong signal.

NanoBiT Assay Using Purified Proteins.

In order to test the LATS NanoBiT biosensor in vitro, a kinase assay was done using purified LgBiT-YAP15 (WT and mutant), 14-3-3-SmBiT and LATS2 as the kinase. The assay was done with two different concentrations of biosensor (100 ng and 5 ng). After 1, 10, 20, 30 min and 1, 2, 4 and 20 h luminescence was measured and also phosphorylation level was checked using WB. Results are shown in FIG. 9 . The upper panel shows the result of NanoBiT assay for YAP15WT and mutant at the two different concentrations of biosensor (5 and 100 ng) as a ratio of luminescence signal in the presence to absence of LATS as a kinase in different time points. The lower panel shows immunoblotting analysis and Ponceau staining of the respective samples from the experiment with 100 ng of biosensor.

Kinase Assay with and without Phosphatase.

To confirm that the biosensor is phosphorylation dependent and works through LATS, lambda phosphatase was used and luminescence as well as phosphorylation was determined. The results show that treating with lambda phosphatase abolishes luminescence. In FIG. 10 the upper panel shows the result of an assay for the biosensor with YAP15 WT or mutant (100 ng) with and without lambda phosphatase after 30 min. The Y axis shows the ratio of luminescence in the presence of LATS and in the absence of LATS. The lower panels show the relative immunoblotting and Ponceau staining for the respective samples

2. YAP-TEAD Biosensor

YAP transcriptionally activates downstream genes by interacting with the TEAD family of transcription factors (i.e., TEAD1-4). To monitor interaction between YAP and TEAD, a NanoBiT split luciferase biosensor was developed that quantifies YAP1 and TEAD1 interaction. This biosensor is based on a YAP fragment (residues 50-171; SEQ ID NO:2)-TEAD1 fragment (residues 194-411; SEQ ID NO:50) complex, in which YAP wraps around the globular structure of TEAD1. FIG. 12 shows a schematic overview of the NanoBiT interaction system of a YAP-TEAD NanoBiT biosensor as described herein. The YAP1 mRNA and amino acid sequences are given in SEQ ID NOs:1 and 2, respectively. The TEAD1 mRNA and protein sequences are given in SEQ ID NOs:49 and 50, respectively. The Large BiT (LgBiT) mRNA and protein sequences are given in SEQ ID NOs:51 and 52, respectively. The Small BiT (SmBiT) mRNA and protein sequences are given in SEQ ID NOs:53 and 54, respectively. The vectors were pcDNA3.1/hygro(+) (SEQ ID NO:9), pcDNA3.1/hygro(+)-Flag (SEQ ID NO:55), and pcDNA3.1/hygro(+)-Myc (SEQ ID NO:56).

Eight NanoBit split luciferase constructs were made using the primers as listed below. The domain structures of the eight constructs are shown in FIG. 11 .

Construct 1:

LgBiT-YAP50-171-Flag (overlapping PCR):

SEQ ID NO:34. B1-Kozak-LgBiT-F primer (41 nucleotides):

SEQ ID NO:35. LgBiT-(GS)-R primer (54 nucleotides):

SEQ ID NO:36. (GS)-YAP50-F primer (69 nucleotides):

SEQ ID NO:37. N1-YAP171-Flag-R primer (63 nucleotides)

Construct 2:

Flag-YAP50-171-LgBiT (overlapping PCR):

SEQ ID NO:38. B1-YAP50-F primer (32 nucleotides):

SEQ ID NO:39. (GS)-YAP171-R primer (68 nucleotides):

SEQ ID NO:40. (GS)-LgBiT-F primer (66 nucleotides):

SEQ ID NO:41. N1-LgBiT-R primer (43 nucleotides):

Construct 3:

SmBiT-YAP50-171-Flag (tandem PCR):

SEQ ID NO:42. B1-Kozak-SmiBiT-(GS)-F primer (98 nucleotides):

SEQ ID NO:36. (GS)-YAP50-F primer (69 nucleotides):

SEQ ID NO:37. N1-YAP171-Flag-R primer (63 nucleotides)

Construct 4:

Flag-YAP50-171-SmBiT (tandem PCR):

SEQ ID NO:38. B1-YAP50-F primer (32 nucleotides)

SEQ ID NO:39. (GS)-YAP171-R primer (68 nucleotides)

SEQ ID NO:43. N1-SmBiT-(GS)-R primer (97 nucleotides):

Construct 5:

LgBiT-TEAD1-194-411-Myc (overlapping PCR):

SEQ ID NO:34. B1-Kozak-LgBiT-F primer (41 nucleotides)

SEQ ID NO:35. LgBiT-(GS)-R primer (54 nucleotides)

SEQ ID NO:44. (GS)-TEAD-194-F primer (73 nucleotides):

SEQ ID NO:45. N1-TEAD411-Myc-R primer (73 nucleotides):

Construct 6:

Myc-TEAD1-194-411-LgBiT (overlapping PCR)

SEQ ID NO:46. B1-TEAD194-F primer (36 nucleotides):

SEQ ID NO:47. GS-TEAD-411-R primer (69 nucleotides):

SEQ ID NO:40. (GS)-LgBiT-F primer (66 nucleotides)

SEQ ID NO:41. N1-LgBiT-R primer (43 nucleotides)

Construct 7:

SmBiT-TEAD1-194-411-Myc (tandem PCR)

SEQ ID NO:42. B1-Kozak-SmiBiT-(GS)-F primer (98 nucleotides)

SEQ ID NO:48. (GS)-TEAD194-F primer (73 nucleotides):

SEQ ID NO:45. N1-TEAD411-Myc-R primer (73 nucleotides)

Construct 8: Myc-TEAD-194-411-SmBiT (tandem PCR)

SEQ ID NO:46. B1-TEAD194-F primer (36 nucleotides)

SEQ ID NO:47. GS-TEAD-411-R primer (69 nucleotides)

SEQ ID NO:43. N1-SmBiT-(GS)-R primer (97 nucleotides)

Cloning.

To make constructs 1 and 5, overlapping PCR was performed using the above primers, and they were inserted into BamH1/Not1 cloning site of pcDNA3.1/hygro. For construct 1, pBiT1.1-N(TK/LgBiT) and full length YAP were used as templates to perform PCR. For construct 5, pBiT1.1-N(TK/LgBiT) and full length TEAD1 were used to perform PCR.

To make constructs 2 and 6, overlapping PCR was performed using the above primers, and they were inserted into BamH1/Not1 cloning site of pcDNA3.1/hygro-Flag/Myc. For construct 2, pBiT1.1-C(TK/LgBiT) and full length YAP were used to perform PCR. For construct 6, pBiT1.1-C(TK/LgBiT) and full length TEAD1 were used to perform PCR.

To make constructs 3 and 7, tandem PCR was performed using the above primers, and they were inserted into BamH1/Not1 cloning site of pcDNA3.1/hygro. For both constructs full length YAP and TEAD1 were used respectively to perform PCR.

To make construct 4 and 8, overlapping PCR was performed using the above primers, and they were inserted into BamH1/Not1 cloning site of pcDNA3.1/hygro-Flag/Myc. For both constructs full length YAP and TEAD1 were used respectively to perform PCR.

SEQ ID NOs:63-70 give the full length sequences for constructs 1-8, respectively, wherein, in each sequence, the underlined portion is the main construct and the rest is the vector.

Validation.

Different combinations of the eight constructs were used in assays in order to find the best orientation for the biosensor. The assays used overexpressed YAP50-171 and TEAD1-194-411 in HEK293T cells lysed with passive lysis buffer. All combinations of SmBiT and LgBiT biosensors worked, but the combination of SmBiT-YAP50-171 and LgBiT-TEAD1-194-411 showed the highest signal and sensitivity (FIG. 13 ).

Discussion

The embodiments and experiments described herein establish the LATS biosensor embodiments as the first LATS biosensor that can accurately monitor LATS kinase activity and intensity of Hippo signaling in vitro and in vivo, and its use in a new bioluminescence (BLI) method. In addition, the embodiments and experiments described herein establish the YAP-TEAD biosensor embodiments as the first biosensor that can accurately monitor YAP and TEAD interaction, which is essential for elucidating the function of YAP in the Hippo pathway. Although BLI is widely used for reporting promoter activity and imaging tumors in mice, few studies have used it to measure protein function at the cellular level and even fewer studies have examined subcellular protein function using bioluminescence microscopy. The ability to detect LATS kinase activity in individual cells and in blood as provided by the embodiments described herein has applications for evaluating heterogeneous dynamics of LATS kinase activity in cell culture as well as for the real-time monitoring of Hippo signaling responses to various drug treatments, and in applications such as detecting Hippo pathway signaling in biological samples such as tissue and blood obtained from subjects. In particular, the results show that a biosensor as described herein may be useful for detecting cancerous cells in biological samples such as tissue. The results of in vivo experiments in mice further illustrate how LATS-BS embodiments may be used to preclinically examine the effects of a variety of drugs on LATS kinase activity in vivo.

A biosensor as described herein may be provided in a kit to measure the Hippo signaling pathway, for use in vitro and in vivo. For example, a kit may include one or more LATS biosensor such as an intermolecular biosensor, intramolecular biosensor, engineered biosensor, or NanoBiT biosensor, and/or a YAP-TEAD biosensor as described herein, optionally with one or more reagents suitable for using the kit in an assay for a specified biological sample or cell type, and instructions for proper use of the kit. The reagent may be, for example, a reagent appropriate for in vitro use or for in vivo use, a buffer, cell lysis buffer, etc.

Example

The following example provides details of the methods used to make and use an intermolecular LATS biosensor as described herein.

1. Determine activity of purified LATS protein and LATS in cells by in vitro luciferase assay (described above and shown in FIGS. 2C, 2D, 3C, 8, and 13 ).

2. Determine interaction of YAP and TEAD in cells by in vitro luciferase assay (described above and shown in FIG. 13 ).

3. Determine LATS kinase activity under various stimuli regulating Hippo signaling by live cell luciferase imaging.

For live cell imaging, LATS-BS or a pGL3-control vector were transfected into HEK293, MDA-MB-231 or A549 cells. After 48 hours, cells were trypsinized and collected in a black, clear bottomed, 96-well plate. 150 μg/mL D-luciferin (D-Luciferin, Potassium Salt, GoldBio #LUCK-250) in media was added to each well 5-10 min before imaging. Exposure time for images was approximately 3 min/plate. Imaging was performed using a LightTools Research system (Synopsys, Ltd., Mountain View, Calif., USA) dark box and a Hamamatsu ORCA-Flash4.0 V2 digital CMOS camera over the course of 20 minutes to establish optimal peak luciferase activity. The bioluminescence of the regions of interest was analyzed for total emission flux using Image-Pro® Plus software (Media Cybernetics, Inc., Rockville, Md., USA).

Experiments were conducted to further validate the LATS intermolecular biosensor and explore potential applications for its use. The LATS-BS responded to numerous signals reported to modulate Hippo pathway activity, including cell confluency, drugs activating Hippo signaling (Forskolin, PI3K inhibitor, PDK inhibitor, F-IBMX, and 2-deoxy-glucose) and Hippo signaling inhibitors (LPA, EGF, Insulin, S1P, and TPA). The LATS-BS is activated by LATS in various cell lines (e.g., A549, MDA-MB231). Notably, in these experiments biosensor activity was measured in both cell lysates and in live cells using luciferase assay and BLI respectively. Collectively, these data illustrate the broad range of potential applications for the LATS-BS in monitoring Hippo pathway activity.

The following compound treatments were used for in vitro luciferase assay and live cells imaging: RAF inhibitor (GW5054, Cayman Chemical, Ann Arbor, Mich., USA), ATR inhibitor (CGK733, Cayman Chemical), PI3K inhibitor 1 (GDC0941, Cayman Chemical), PI3K inhibitor 2 (LY294002, Cayman Chemical), PDK inhibitor (GSK2334470, Cayman Chemical)—10 μM for 4 hours; EGF-100 ng/mL for 1 hour; insulin (Sigma #91077C)—10 μg/ml for 1 hour, F/IBMX (Forskolin, Cayman Chemical/IBMX, Cayman Chemical)—0.1-10 μM for Forskolin and 100 μM for IBMX for 1 hour; L-α-lysophosphatidic acid (LPA) (Sigma #L7260)—0.1-10 μM for 1 hour, sphingosine1-phosphophate (S1P)—1 μM for 1 hour; 12-O-tetradecanoylphorbol-13-acetate (TPA) (#41745; Cell Signaling Technology, Inc., Danvers, Mass., USA)—5 nM for 1 hour; 2-deoxy glucose (#D8375, Sigma-Aldrich Canada Co., Oakville, Ontario, Canada)—25 mM for 1 hour. The results are shown in FIG. 14 .

4. Determine subcellular LATS kinase activity by bioluminescent microscopy.

Using the intermolecular LATS-BS, a new method was developed for the Olympus LV200 Bioluminescence Imager, and LATS kinase activity was visualized and quantified at the individual cell level in cancer cell lines. 3.5 mM D-luciferin was added to the media culturing HEK293A, A549 or MDA-MB231 cells stably expressing LATS-BS at 5-10 min before imaging. Images were captured using Olympus LV200 Bioluminescence Imager with exposure times ranging from 30 seconds (HEK293A) to 10 min (MDA-MB-231, A549). The results are shown in FIG. 15 . The difference in biosensor signal intensity among individual cells represents altered endogenous LATS kinase activity rather than differential LATS-BS expression levels since only the LATS-phosphorylated fraction of LATS-BS should emit bioluminescence. In addition, data showed that both the levels and subcellular localization of LATS-BS bioluminescence (cytoplasm where LATS is expressed) and GFP (control, nucleus/cytoplasm) were different in the same cell. This technology also allowed comparison of the heterogeneity of LATS kinase activity among cancer cell lines by assessing the distribution of luciferase activity. Further, and of particular significance, using biophotonics BLI, LATS kinase activity was detected in vivo in mice. The subcellular activity of LATS kinase can be also visualized by bioluminescent imaging.

5. Measuring LATS kinase activity in mice by in vivo luciferase imaging.

Further, and of particular significance, using biophotonics BLI, LATS kinase activity was detected in vivo in mice. All mouse procedures were approved by the Queen's University Animal Care Committee (UACC) and performed in accordance with institutional policies. To visualize LATS kinase activity in vivo, 12-week-old female BALB/c mice were anesthetized by exposure to 1-3% isoflurane. 3×106 HEK293 cells transfected with an intermolecular LATS-BS alone (LATS−) or together with LATS (LATS+) were suspended in 100 μL of sterile PBS and injected into the mammary fat pad. Two days after the injection, post-surgery mice received 150 mg/kg of D-luciferin (Cedarlane) dissolved in PBS by intraperitoneal injection. Imaging of ventral view was performed using a LightTools Research system (Encinitas, Calif.) dark box and a Hamamatsu ORCA-Flash4.0 V2 digital CMOS camera over a course of 30 minutes to establish optimal peak luciferase activity. Pseudo-colored parametric overlays of BLI with anatomical reference images were dynamically constructed for each individual animal at comparative time points. The bioluminescence (BLI) of the regions of interest (ROI) was then analyzed for total emission flux using Image Pro Plus software. The results are shown in FIG. 16 , where the arrow (right panel) points to the area where high intensity luminescence (red in heatmap) was detected.

6. Identifying novel regulators of LATS by a kinase inhibitor screen.

The intermolecular LATS-BS was used to search for novel kinases regulating Hippo signaling with a small-scale kinase inhibitor screen. The LATS-BS was transfected into HEK293A. Cells were passed into a 384-well plate the following day. 48 hours after transfection, cells were treated with the Tocriscreen Kinase Inhibitor Toolbox (Tocris Bioscience #3514) with each drug administered at 10 μM in DMSO for 4 hours in duplicate. Biosensor activity was then measured by luciferase assay. Fold change ratios were generated by comparing biosensor activity for each drug with that of DMSO-treated controls. The screening schematic and results are shown in FIGS. 17A and 17B, respectively. Of 80 kinase inhibitors screened, six kinase inhibitors activated the biosensor (i.e., inhibitors of VEGFR, MEK, GSK-3, PKB/Akt, EGFR, and CDK) while six inhibitors reduced the biosensor signal (i.e., inhibitors of TrkA, Broad, SYK, ATR/ATM, CHK1, and SGK). From these candidate LATS regulators, VEGFR1/2, GSK-3a/b, CDK4, TrkA, SYK, Broad, and SGK are novel. The screen results were confirmed by luciferase assays using the LATS-BS and an STBS-luciferase reporter that measures the transactivating function of YAP/TAZ32. The kinase inhibitors had the opposite effects on LATS-BS and STBS reporter, suggesting that the screen had identified true regulators of Hippo signaling. It is expected that future large-scale screens using the LATS-BS will identify additional new activators or inhibitors of the Hippo signaling pathway.

All cited publications are incorporated herein by reference in their entirety.

Sequences SEQ ID NO: 1. Human YAP1 (yes-associated protein beta) isoform 2L mRNA (1,401 nucleotides) (accession number: AB567720) ATGGATCCCGGGCAGCAGCCGCCGCCTCAACCGGCCCCCCAGGGCCAAGGGCAGCCGCCTTCGC AGCCCCCGCAGGGGCAGGGCCCGCCGTCCGGACCCGGGCAACCGGCACCCGCGGCGACCCAGGC GGCGCCGCAGGCACCCCCCGCCGGGCATCAGATCGTGCACGTCCGCGGGGACTCGGAGACCGAC CTGGAGGCGCTCTTCAACGCCGTCATGAACCCCAAGACGGCCAACGTGCCCCAGACCGTGCCCA TGAGGCTCCGGAAGCTGCCCGACTCCTTCTTCAAGCCGCCGGAGCCCAAATCCCACTCCCGACA GGCCAGTACTGATGCAGGCACTGCAGGAGCCCTGACTCCACAGCATGTTCGAGCTCATTCCTCT CCAGCTTCTCTGCAGTTGGGAGCTGTTTCTCCTGGGACACTGACCCCCACTGGAGTAGTCTCTG GCCCAGCAGCTACACCCACAGCTCAGCATCTTCGACAGTCTTCTTTTGAGATACCTGATGATGT ACCTCTGCCAGCAGGTTGGGAGATGGCAAAGACATCTTCTGGTCAGAGATACTTCTTAAATCAC ATCGATCAGACAACAACATGGCAGGACCCCAGGAAGGCCATGCTGTCCCAGATGAACGTCACAG CCCCCACCAGTCCACCAGTGCAGCAGAATATGATGAACTCGGCTTCAGCCATGAACCAGAGAAT CAGTCAGAGTGCTCCAGTGAAACAGCCACCACCCCTGGCTCCCCAGAGCCCACAGGGAGGCGTC ATGGGTGGCAGCAACTCCAACCAGCAGCAACAGATGCGACTGCAGCAACTGCAGATGGAGAAGG AGAGGCTGCGGCTGAAACAGCAAGAACTGCTTCGGCAGGCAATGCGGAATATCAATCCCAGCAC AGCAAATTCTCCAAAATGTCAGGAGTTAGCCCTGCGTAGCCAGTTACCAACACTGGAGCAGGAT GGTGGGACTCAAAATCCAGTGTCTTCTCCCGGGATGTCTCAGGAATTGAGAACAATGACGACCA ATAGCTCAGATCCTTTCGTTAACAGTGGCACCTATCACTCTCGAGATGAGAGTACAGACAGTGG ACTAAGCATGAGCAGCTACAGTGTCCCTCGAACCCCAGATGACTTCCTGAACAGTGTGGATGAG ATGGATACAGGTGATACTATCAACCAAAGCACCCTGCCCTCACAGCAGAACCGTTTCCCAGACT ACCTTGAAGCCATTCCTGGGACAAATGTGGACCTTGGAACACTGGAAGGAGATGGAATGAACAT AGAAGGAGAGGAGCTGATGCCAAGTCTGCAGGAAGCTTTGAGTTCTGACATCCTTAATGACATG GAGTCTGTTTTGGCTGCCACCAAGCTAGATAAAGAAAGCTTTCTTACATGGTTATAG SEQ ID NO: 2. Human YAP1 isoform 2L protein (504 amino acids) MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGDSETD LEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTPQHVRAHSS PASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMAKTSSGQRYFLNH IDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAMTQDGEIYYINHKNKTT SWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNSNQQQQMRLQQLQMEKERLRL KQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGGTQNPVSSPGMSQELRTMTTNSSDP FLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSVDEMDTGDTINQSTLPSQQNRFPDYLEAI PGTNVDLGTLEGDGMNIEGEELMPSLQEALSSDILNDMESVLAATKLDKESFLTWL SEQ ID NO: 3. Human 14-3-3 protein theta mRNA (738 nucleotides) (accession number: P27348) ATGGAGAAGACTGAGCTGATCCAGAAGGCCAAGCTGGCCGAGCAGGCCGAGCGCTACGACGACA TGGCCACCTGCATGAAGGCAGTGACCGAGCAGGGCGCCGAGCTGTCCAACGAGGAGCGCAACCT GCTCTCCGTGGCCTACAAGAACGTGGTCGGGGGCCGCAGGTCCGCCTGGAGGGTCATCTCTAGC ATCGAGCAGAAGACCGACACCTCCGACAAGAAGTTGCAGCTGATTAAGGACTATCGGGAGAAAG TGGAGTCCGAGCTGAGATCCATCTGCACCACGGTGCTGGAATTGTTGGATAAATATTTAATAGC CAATGCAACTAATCCAGAGAGTAAGGTCTTCTATCTGAAAATGAAGGGTGATTACTTCCGGTAC CTTGCTGAAGTTGCGTGTGGTGATGATCGAAAACAAACGATAGATAATTCCCAAGGAGCTTACC AAGAGGCATTTGATATAAGCAAGAAAGAGATGCAACCCACACACCCAATCCGCCTGGGGCTTGC TCTTAACTTTTCTGTATTTTACTATGAGATTCTTAATAACCCAGAGCTTGCCTGCACGCTGGCT AAAACGGCTTTTGATGAGGCCATTGCTGAACTTGATACACTGAATGAAGACTCATACAAAGACA GCACCCTCATCATGCAGTTGCTTAGAGACAACCTAACACTTTGGACATCAGACAGTGCAGGAGA AGAATGTGATGCGGCAGAAGGGGCTGAAAACTAA SEQ ID NO: 4. Human 14-3-3 protein theta (245 amino acids) MEKTELIQKAKLAEQAERYDDMATCMKAVTSQGAELSNSERNLLSVAYKNVVGGRRSAWRVISS IEQKTDTSDKKLQLIKDYREKVESELRSICTTVLELLDKYLIANATHPESKVFYLKMKGDYFRY LAEVACGDDRKQTIDNSQGAYQEAFDISKKEMQPTHPIRLGLALNFSVFYYEILNNPELACTLA KTAFDEAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDSAGEECDAAEGAEN SEQ ID NO: 5. Firefly (Photinus pyralis) luciferase mRNA (1,653 nucleotides) ATGGAAGACGCCAAAAACATAAAGAAAGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACCG CTGGAGAGCAACTGCATAAGGCTATGAAGAGATACGCCCTGGTTCCTGGAACAATTGCTTTTAC AGATGCACATATCGAGGTGGACATCACTTACGCTGAGTACTTCGAAATGTCCGTTCGGTTGGCA GAAGCTATGAAACGATATGGGCTGAATACAAATCACAGAATCGTCGTATGCAGTGAAAACTCTC TTCAATTCTTTATGCCGGTGTTGGGCGCGTTATTTATCGGAGTTGCAGTTGCGCCCGCGAACGA CATTTATAATGAACGTGAATTGCTCAACAGTATGGGCATTTCGCAGCCTACCGTGGTGTTCGTT TCCAAAAAGGGGTTGCAAAAAATTTTGAACGTGCAAAAAAAGCTCCCAATCATCCAAAAAATTA TTATCATGGATTCTAAAACGGATTACCAGGGATTTCAGTCGATGTACACGTTCGTCACATCTCA TCTACCTCCCGGTTTTAATGAATACGATTTTGTGCCAGAGTCCTTCGATAGGGACAAGACAATT GCACTGATCATGAACTCCTCTGGATCTACTGGTCTGCGTAAAGGTGTCGCTCTGCCTCATAGAA CTGCCTGCGTGAGATTCTCGCATGCCAGAGATCCTATTTTTGGCAATGAAATCATTCCGGATAC TGCGATTTTAAGTGTTGTTGCATTCCATCACGGTTTTGGAATGTTTACTACACTCGGATATTTG ATATGTGGATTTCGAGTCGTCTTAATGTATAGATTTGAAGAAGACCTGTTTCTGAGGAGCCTTC AGGATTACAAGATTCAAAGTGCGCTGCTGGTGCCAACCCTATTCTCCTTCTTCGCCAAAAGCAC TCTGATTGACAAATACGATTTATCTAATTTACACGAAATTGCTTCTGGTGGCGCTCCCCTCTCT AAGGAAGTCGGGGAAGCGGTTGCCAAGAGGTTCCATCTGCCAGGTATCAGGCAAGGATATGGGC TCACTGAGACTACATCAGCTATTCTGATTACACCCGAGGGGGATGATAAACCGGGCGCGGTCGG TAAAGTTGTTCCATTTTTTGAAGCGAAGGTTGTGGATCTGGATACCGGGAAAACGCTGGGCGTT AATCAAAGAGGCGAACTGTGTGTGAGAGGTCCTATGATTATGTCCGGTTATGTAAACAATCCGG AAGCGACCAACGCCTTGATTGACAAGGATGGATGGCTACATTCTGGAGACATAGCTTACTGGGA CGAAGACGAACACTTCTTCATCGTTGACCGCCTGAAGTCTCTGATTAAGTACAAAGGCTATCAG GTGGCTCCCGCTGAATTGGAATCCATCTTGCTCCAACACCCCAACATCTTCGACGCAGGTGTCG CAGGTCTTCCCGACGATGACGCCGGTGAACTTCCCGCCGCCGTTGTTGTTTTGGAGCACGGAAA GACGATGACGGAAAAAGAGATCGTGGATTACGTCGCCAGTCAAGTAACAACCGCGAAAAAGTTG CGCGGAGGAGTTGTGTTTGTGGACGAAGTACCGAAAGGTCTTACCGGAAAACTCGACGCAAGAA AAATCAGAGAGATCCTCATAAAGGCCAAGAAGGGCGGAAAGATCGCCGTGTAA SEQ ID NO: 6. Firefly (Photinus pyralis) luciferase protein (555 amino acids) MEDAKNIKKGPAPFYPLEDGTAGEQLHKAMKRYALVPGTIAFTDAHIEVDITYAEYFEMSVRLA EAMKRYGLNTNHRIVVCSENSLQFFMPVLGALFIGVAVAPANDIYNERELLNSMGISQPTVVFV SKKGLQKILNVQKKLPIIQKIIIMDSKTDYQGFQSMYTFVTSHLPPGFKEYDFVPESFDRDKTI ALIMNSSGSTGLPKGVALPHRTACVRFSHARDPIFGNQIIPDTAILSVVPFHHGFGMFTTLGYL ICGFRVVLMYRFEEELFLRSLQDYKIQSALLVPTLFSFFAKSTLIDKYDLSNLHEIASGGAPLS KEVGEAVAKRFHLPGIRQGYGLTETTSAILITPEGDDKPGAVGKVVPFFEAKVVDLDTGKTLGV NQRGELCVRGPMIMSGYVNNPEATNALIDKDGWLHSGDIAYWDEDEHFFIVDRLKSLIKYKGYQ VAPAELESILLQHPNIFDAGVAGLPDDDAGELPAAVVVLEKGKTMTEKEIVDYVASQVTTAKKL RGGVVFVDEVPKGLTGKLDARKIREILIKAKKGGKIAV SEQ ID NO: 7. YAP15 S127 wildtype (WT) protein fragment (15 amino acids) PQHVRHASSPASLQL SEQ ID NO: 8. YAP15 A127 mutant protein fragment (15 amino acids) PQHVRHAASPASLQL SEQ ID NO: 9. pcDNA3.1/hygro(+) vector (5,597 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGCGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTGAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCTGC AGATATCCAGCACAGTGGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCT CGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCT GGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGT AGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACA ATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGG CTCTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACG CGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCT TTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCG ATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGG CCAT0GCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGAC TCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGAT TTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAA TTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTAT GCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCGCCAGGCTCCCCAGCAGGC AGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCGA TCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTAT TTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTT GGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGC ACGTGATGAAAAAGCCTGAACTCACCGCGACGTCTGTCGAGAAGTTTCTGATCGAAAAGTTCGA CAGCGTCTCCGACCTGATGCAGCTCTCGGAGGGCGAAGAATCTCGTGCTTTCAGCTTCGATGTA GGAGGGCGTGGATATGTCCTGCGGGTAAATAGCTGCGCCGATGGTTTCTACAAAGATCGTTATG TTTATCGGCACTTTGCATCGGCCGCGCTCCCGATTCCGGAAGTGCTTGACATTGGGGAATTCAG CGAGAGCCTGACCTATTGCATCTCCCGCCGTGCACAGGGTGTCACGTTGCAAGACCTGCCTGAA ACCGAACTGCCCGCTGTTCTGCAGCCGGTCGCGGAGGCCATGGATGCGATCGCTGCGGCCGATC TTAGCCAGACGAGCGGGTTCGGCCCATTCGGACCGCAAGGAATCGGTCAATACACTACATGGCG TGATTTCATATGCGCGATTGCTGATCCCCATGTGTATCACTGGCAAACTGTGATGGACGACACC GTCAGTGCGTCCGTCGCGCAGGCTCTCGATGAGCTGATGCTTTGGGCCGAGGACTGCCCCGAAG TCCGGCAGCTCGTGCACGCGGATTTCGGCTCCAACAATGTCCTGACGGACAATGGCCGGATAAC AGCGGTCATTGACTGGAGCGAGGCGATGTTCGGGGATTCCCAATACGAGGTCGCCAACATGTTC TTCTGGAGGCCGTGGTTGGCTTGTATGGAGCAGCAGACGCGCTACTTCGAGCGGAGGCATCCGG AGCTTGCAGGATCGCCGCGGCTCCGGGCGTATATGCTCCGCATTGGTCTTGACCAACTCTATCA GAGCTTGGTTGACGGCAATTTGGATGATGCAGCTTGGGCGCAGGGTCGATGCGACGGAATCGTC CGATCCGGAGCCGGGACTGTCGGGCGTACAGAAATCGCCCGCAGAAGCGCGGCCGTGTGGACCG ATGGCTGTGTAGAAGTACTCGCCGATAGTGGAAAGCGACGCCCCAGCACTCGTCCGAGGGCAAA GGAATAGCACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGA ATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTGATGCTGGAGTTCTTCG CCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTT CACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCT TATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTC CTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAA AGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCGCGCTTTC CAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTT TGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCG GCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCA GGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGGCGCGTTGCTGG CGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTG GCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCT CCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGC TTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTG TGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCC AACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGA GGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAAC AGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGA TCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAA AAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAA CTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAAT TAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAAT GCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACT CCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATA CCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCG AGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCGAGTCTATTAATTGTTGCCGGGAAGC TAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTG GTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTA CATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATG CCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTA TGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAAC TTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTG TTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCA CCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGAC ACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTAT TGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCA CATTTCCCCGAAAAGTGCCACCTGAGGTC SEQ ID NO: 10. B1-Kozak-Nluc-F primer (41 nucleotides) CTGGATCCGCCGCCACCATGGAAGACGCCAAAAACATG SEQ ID NO: 11. Nluc-416-Yap-15-S127-(GGAGG)-R primer (84 nucleotides) TTACAACTGCAGAGAAGCTGGAGAGGAATGAGCTCGAACATGCTGTGGGCCTCCAGCTCCTCCT CCATCCTTGTCAATCAAGGC SEQ ID NO: 12. N1-Yap-5-Overlapping PCR-R primer (36 nucleotides) ATGATACTGCGGCCGCTTACAACTGCAGAGAAGCTG SEQ ID NO: 13. B1-Kozak-14-3-3-F primer (38 nucleotides) CTGGATCCGCCGCCACCATGGAGAAGACTGAGCTGATC SEQ ID NO: 14. (GGGGS)2-14-3-3-R primer (51 nucleotides) ACTACCTCCTCCTCCACTACCTCCTCCTCCGTTTTCAGCCCCTTCTGCCGC SEQ ID NO: 15. (GGGGS)2-Cluc394-F primer (39 nucleotides) GGTAGTGGAGGAGGAGGTAGTGGTCCTATGATTATGTCC SEQ ID NO: 16. N1-Cluc-R primer (34 nucleotides) ATGAAACTGCGGCCGCTTACACGGCGATCTTTCC SEQ ID NO: 17. Nluc398-15-S127-(GGAGG)-R primer (81 nucleotides) CAACTGCAGAGAAGCTGGAGAGGAATGAGCTCGAACATGCTGTGGGCCTCCAGCTCCTCCCATA ATCATAGGACCTCTCAC SEQ ID NO: 18. Yap15-S127-Cluc394-F primer (42 nucleotides) TCTCCAGCTTCTCTGCAGTTGGGTCCTATGATTATGTCCGGT SEQ ID NO: 19. N1-Yap15-S127-Cluc443 (engineered C-terminus of luciferase)-R primer (86 nucleotides) ATGAAACTGCGGCCGCTTACAACTGCAGAGAAGCTGGAGAGGAATGAGCTCGAACATGCTGTGG CTTCTTGGCCTTTATGAGGATC SEQ ID NO: 20. EcoR1-YAP-S127-BglII-S primer (55 nucleotides) AATTCACCACAGCATGTTCGAGGTCATTCCTCTCCAGCTTCTCTGCAGTTGTGAA SEQ ID NO: 21. ECoR1-YAP-S127-BglII-AS primer (55 nucleotides) GATCTTCACAACTGCAGAGAAGCTGGAGAGGAATGAGCTCGAACATGCTGTGGTG SEQ ID NO: 22. EcoR1-YAP-A127-BglII-S primer (55 nucleotides) AATTCACCACAGCATGTTCGAGCTCATGCGTCTCCAGCTTCTCTGCAGTTGTGAA SEQ ID NO: 23. ECoR1-YAP-A127-BglII-AS primer (55 nucleotides) GATCTTCACAACTGCAGAGAAGCTGGAGACGCATGAGCTCGAACATGCTGTGGTG SEQ ID NO: 24. BglII-14-3-3-F primer (31 nucleotides) GGAAGATCTAATGGAGAAGACTGAGCTGATC SEQ ID NO: 25. ECoR1-14-3-3-R primer (34 nucleotides) CGCCGGAATTCCCGTTTTCAGCCCCTTCTGCCGC SEQ ID NO: 26. pBiT 1.1 N (TK-Larg BiT) whole vector (3,858 nucleotides) GGCCTAACTGGCCGGTACCTGAGTCTAAATGAGTCTTCGGACCTCGCGGGGGCCGCTTAACCGG TGGTTAGGGTTTGTCTGACGCGGGGGGAGGGGGAAGGAACGAAACACTCTCATTCGGAGGCGGC TCGGGGTTTGGTCTTGGTGGCCACGGGCACGCAGAAGAGCGCCGCGATCCTCTTAAGCACCCCC CCGCCCTCCGTGGAGGCGGGGGTTTGGTCGGCGGGTGGTAACTGGCGGGCGGCTGACTCGGGCG GGTCGCGCGCCCCAGAGTGTGACCTTTTCGGTCTGCTCGCAGACCCCCGGGCGGCGCCGCCGCG GCGGCGACGGGCTCGCTGGGTCCTAGGCTCCATGGGGACCGTATACGTGGACAGGCTCTGGAGC ATCCGCACGACTGCGGTGATATTAGCGGAGACCTTCTGCGGGACGAGCCGGGTCACGCGGCTGA CGCGGAGCGTCGGTTGGGCGACAAACAGCAGGACGGGGCACAGGTACACTATCTTGTCACCCGG AGGCGCGAGGGACTGCAGGAGCTTCAGGGAGTGGCGCAGCTGCTTCATCCCCGTGGCCCGTTGC TCGCGTTTGCTGGCGGTGTCCCCGGAAGAAATATATTTGCATGTCTTTAGTTCTATGATGACAC AAACCCCGCCCAGCGTCTTGTCATTGGCGAAGTCGAACACGCAGATGCAGTCGGGGCGGCGCGG TCCCAGGTCCACTTCGCATATTAAGGTGACGCGTGTGGCCTCGAACACCGAGCGACCCTGCAGC GACCCGCTTAAAAGCTTGGCAATCCGGTACTGTTGGTAAAGCCACCATGGTCTTCACACTCGAA GATTTCGTTGGGGACTGGGAACAGACAGCCGCCTACAACCTGGACCAAGTCCTTGAACAGGGAG GTGTGTCCAGTTTGCTGCAGAATCTCGCCGTGTCCGTAACTCCGATCCAAAGGATTGTCCGGAG CGGTGAAAATGCCCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGCCGAC CAAATGGCCCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGG TGATCCTGCCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGCTGAACTATTTCGG ACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGG AACGGCAACAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCTCCATGCTGTTCCGAGTAA GCATCAACAGTGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGGTCGAGCGGTGGAGCTCA GGGGAATTCAGTCTAAGCTAGCAGATCTTCTAGAGTCGGGGCGGCCGGCCGCTTCGAGCAGACA TGATAAGATAGATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTAT TTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGTTAAC AACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAGGTTTTTTAAAGCA AGTAAAACCTCTACAAATGTGGTAAAATCGATAAGGATCCGTCGACCGATGCCCTTGAGAGCCT TCAACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTCGCCGCACTTATGACTGT CTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTTCCGCTTCCTCGCTCACTGA CTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGG TTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCA GGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCA CAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTT CCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCG CCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGT GTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCC TTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAG CCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTG GCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACC TTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTT TTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTC TACGGGGTCTGAGGCTCAGTGGAACGAAAAGTCAGGTTAAGGGATTTTGGTCATGAGATTATCA AAAAGGATCTTCACCTAGATCCTTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATA ATGAGTAAACTTGGTCTGACAGCGGCCGCAAATGCTAAACCACTGCAGTGGTTACCAGTGCTTG ATCAGTGAGGCACCGATCTCAGCGATCTGCCTATTTCGTTCGTCCATAGTGGCCTGACTCCCCG TCGTGTAGATCACTAGGATTCGTGAGGGCTTAGCATCAGGCCCCAGCGCAGCAATGATGCCGCG AGAGCCGCGTTCACCGGCCCCCGATTTGTCAGCAATGAACCAGCCAGCAGGGAGGGCCGAGCGA AGAAGTGGTCCTGCTACTTTGTCCGCCTCCATCCAGTCTATGAGCTGCTGTCGTGATGCTAGAG TAAGAAGTTCGCCAGTGAGTAGTTTCCGAAGAGTTGTGGCCATTGCTACTGGCATCGTGGTATC ACGCTCGTCGTTCGGTATGGCTTCGTTCAACTCTGGTTCCCAGCGGTCAAGCCGGGTCACATGA TCACCCATATTATGAAGAAATGCAGTCAGCTCCTTAGGGCCTCCGATCGTTGTCAGAAGTAAGT TGGCCGCGGTGTTGTCGCTCATGGTAATGGCAGCACTACACAATTCTCTTACCGTCATGGCATC CGTAAGATGCTTTTCCGTGACCGGCGAGTACTCAACCAAGTCGTTTTGTGAGTAGTGTATACGG CGACCAAGCTGCTCTTGCCCGGCGTGTATACGGGACAACACCGCGCCACATAGCAGTACTTTGA AAGTGCTCATCATCGGGAATCGTTCTTCGGGGCGGAAAGACTCAAGGATCTTGCCGCTATTGAG ATCCAGTTCGATATAGCCCACTCTTGCACCCAGTTGATCTTCAGCATCTTTTACTTTCACCAGC GTTTCGGGGTGTGCAAAAACAGGCAAGCAAAATGCCGCAAAGAAGGGAATGAGTGCGACACGAA AATGTTGGATGCTCATACTCGTCCTTTTTCAATATTATTGAAGCATTTATGAGGGTTACTAGTA CGTCTCTCAAGGATAAGTAAGTAATATTAAGGTACGGGAGGTATTGGACAGGCCGCAATAAAAT ATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGAATCGATAGTACTAACATACGCT CTCCATCAAAACAAAACGAAACAAAACAAACTAGCAAAATAGGCTGTCCCCAGTGCAAGTGCAG GTGCCAGAACATTTCTCT SEQ ID NO: 27. pBiT 2.1 C (TK-SmBiT) whole vector (3,423  nucleotides) GGCCTAACTGGCCGGTACCTGAGTCTAAATGAGTCTTCGGACCTCGCGGGGGCCGCTTAAGCGG TGGTTAGGGTTTGTCTGACGCGGGGGGAGGGGGAAGGAACGAAACACTCTCATTCGGAGGCGGC TCGGGGTTTGGTCTTGGTGGCCACGGGCACGCAGAAGAGCGCCGCGATCCTCTTAAGCACCCCC CCGCCCTCCGTGGAGGCGGGGGTTTGGTCGGCGGGTGGTAACTGGCGGGCCGCTGACTCGGGCG GGTCGCGCGCCCCAGAGTGTGACCTTTTCGGTCTGCTCGGAGACCCCCGGGCGGCGCCGCCGCG GCGGCGACGGGCTCGCTGGGTCCTAGGCTCCATGGGGACCGTATACGTGGACAGGCTCTGGAGC ATCCGCACGACTGCGGTGATATTACCGGAGACCTTGTGCGGGACGAGCCGGGTCACGCGGCTGA CGCGGAGCGTCCGTTGGGCGACAAACACCAGGACGGGGCACAGGTACACTATCTTGTCACCCGG AGGCGCGAGGGACTGCAGGAGCTTCAGGGAGTGGCGCAGCTGCTTCATCCCCGTGGCCCGTTGC TCGCGTTTGCTGGCGGTGTCCCCGGAAGAAATATATTTGCATGTCTTTAGTTCTATGATGACAC AAACCCCGCCCAGCGTCTTGTCATTGGCGAAGTCGAACACGCAGATGCACTCGGGGCGGCGCGG TCCCAGGTCCACTTCGCATATTAAGGTGACGCGTGTGGCCTCGAACACCGAGCGACCCTGCAGC GACCCGCTTAAAAGCTTGGCAATCCGGTACTGTGGTAAAGCCACCAGATCTGCTAGCGATCGCC TAAGTGGGAGCTCAGGGGAATTCTGGCTCGAGCGGTGGTGGCGGGAGCGGAGGTGGAGGGTCGT CAGGTGTGACCGGCTACCGGCTGTTCGAGGAGATTCTGTAATCTAGAGTCGGGGCGGCCGGCGG CTTCGAGCAGACATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAA AAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAA TAAACAAGTTAACAACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAG GTTTTTTAAAGCAAGTAAAAGCTCTACAAATGTGGTAAAATCGATAAGGATGCGTCGACCGATG CCCTTGAGAGCCTTCAACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTCGCCG CAGTTATGACTGTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTTCCGCTT CCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAA GGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGC CAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCC CTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAG ATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACC GGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGT ATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCC CGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCG CCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGT TCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCT GAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGT AGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATC CTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGT CATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCA ATCTAAAGTATATATGAGTAAACTTGGTCTGACAGCGGCCGCAAATGCTAAACCACTGCAGTGG TTACCAGTGCTTGATCAGTGAGGCACCGATCTCAGCGATCTGCCTATTTCGTTCGTCCATAGTG GCCTGACTCCCCGTCGTGTAGATCACTACGATTCGTGAGGGCTTACCATCAGGCCCCAGCGCAG CAATGATGCCGCGAGAGCCGCGTTCACCGGCCCCCGATTTGTCAGCAATGAACCAGCCAGCAGG GAGGGCCGAGCGAAGAAGTGGTCCTGCTACTTTGTCCGCCTCCATCCAGTCTATGAGCTGCTGT CGTGATGCTAGAGTAAGAAGTTCGCCAGTGAGTAGTTTCCGAAGAGTTGTGGCCATTGCTACTG GCATGGTGGTATCACGCTCGTCGTTCGGTATGGCTTCGTTCAACTCTGGTTCCCAGCGGTCAAG CCGGGTCACATGATCACCCATATTATGAAGAAATGCAGTCAGCTCCTTAGGGCCTCCGATCGTT GTCAGAAGTAAGTTGGCCGCGGTGTTGTCGCTCATGGTAATGGCAGCACTACACAATTCTCTTA CCGTCATGCCATCCGTAAGATGCTTTTCCGTGACCGGCGAGTACTCAACCAAGTCGTTTTGTGA GTAGTGTATACGGCGACCAAGCTGCTGTTGCCCGGCGTCTATACGGGACAACACCGCGCCACAT AGCAGTACTTTGAAAGTGCTCATCATCGGGAATCGTTCTTCGGGGCGGAAAGACTCAAGGATCT TGCCGCTATTGAGATCCAGTTCGATATAGCCCACTCTTGCACCCAGTTGATCTTCAGCATCTTT TACTTTCACCAGCGTTTCGGGGTGTGCAAAAACAGGCAAGCAAAATGCCGCAAAGAAGGGAATG AGTGCGACACGAAAATGTTGGATGCTCATACTCGTCCTTTTTCAATATTATTGAAGCATTTATC AGGGTTACTAGTACGTCTCTCAAGGATAAGTAAGTAATATTAAGGTACGGGAGGTATTGGACAG GCCGCAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGAATCGATAGT ACTAACATACGCTCTCCATCAAAACAAAACGAAACAAAACAAACTAGCAAAATAGGCTGTCCCC AGTGCAAGTGCAGGTGCCAGAACATTTCTCT SEQ ID NO: 28. NdeI-LgBiT-YAP15-F primer (38 nucleotides) GGAATTCATATGATGGTCTTCACACTCGAAGATTTCGT SEQ ID NO: 29. B1-LgBiT-YAP15-R primer (40 nucleotides) CGCGGGATCCTTACAACTGCAGAGAAGCTGGAGAGGAATG SEQ ID NO: 30. B1-LgBiT-YAP15A127-R primer (43 nucleotides) CGCGGGATCCTTACAACTGCAGAGAAGCTGGAGACGCATGAGC SEQ ID NO: 31. NdeI-14-3-3-SmBiT-F primer (38 nucleotides) GGAATTCATATGATGGAGAAGACTGAGCTGATCCAGAA SEQ ID NO: 32. B1-14-3-3-SmBiT-R primer (40 nucleotides) CGCGGGATCCTTACAGAATCTCCTCGAACAGCCGGTAGCC SEQ ID NO: 33. pET 16b (6 his N-terminal) whole vector (5,711 nucleotides) TTCTCATGTTTGACAGCTTATCATCGATAAGCTTTAATGCGGTAGTTTATCACAGTTAAATTGC TAACGCAGTCAGGCACCGTGTATGAAATCTAACAATGCGCTCATCGTCATCCTCGGCACCGTCA CCCTGGATGCTGTAGGCATAGGCTTGGTTATGCCGGTACTGCCGGGCCTCTTGCGGGATATCCG GATATAGTTCCTCCTTTCAGCAAAAAACCCCTCAAGACCCGTTTAGAGGCCCCAAGGGGTTATG CTAGTTATTGCTCAGCGGTGGCAGCAGCCAACTCAGCTTCCTTTCGGGCTTTGTTAGCAGCCGG ATCCTCGAGCATATGACGACCTTCGATATGGCCGCTGCTGTGATGATGATGATGATGATGATGA TGATGGCCCATGGTATATCTCCTTCTTAAAGTTAAACAAAATTATTTCTAGAGGGGAATTGTTA TCCGCTCACAATTCCCCTATAGTGAGTCGTATTAATTTCGCGGGATCGAGATCTCGATCCTCTA CGCCGGACGCATCGTGGCCGGCATCACCGGCGCCACAGGTGCGGTTGCTGGCGCCTATATCGCC GACATCACCGATGGGGAAGATCGGGCTCGCCACTTCGGGCTCATGAGCGCTTGTTTCGCCGTGG GTATGGTGGCAGGCCCCGTGGCCGGGGGACTGTTGGGCGCCATCTCCTTGCATGCACCATTCCT TGCGGCGGCGGTGCTCAACGGCCTCAACCTACTACTGGGCTGCTTCCTAATGCAGGAGTCGCAT AAGGGAGAGCGTCGAGATCCCGGACACCATCGAATGGCGCAAAACCTTTCGCGGTATGGCATGA TAGCGCCCGGAAGAGAGTCAATTCAGGGTGGTGAATGTGAAACCAGTAACGTTATACGATGTCG CAGAGTATGCCGGTGTCTCTTATCAGACCGTTTCCCGCGTGGTGAACCAGGCCAGCCACGTTTC TGCGAAAACGCGGGAAAAAGTGGAAGCGGCGATGGCGGAGCTGAATTACATTCCCAACCGCGTG GCACAACAACTGGCGGGCAAACAGTCGTTGCTGATTGGCGTTGCCACCTCCAGTCTGGCCCTGC ACGCGCCGTCGCAAATTGTCGCGGCGATTAAATCTCGCGCCGATCAACTGGGTGCCAGCGTGGT GGTGTCGATGGTAGAACGAAGCGGCGTCGAAGCCTGTAAAGCGGCGGTGCACAATCTTCTCGCG CAACGCGTCAGTGGGCTGATCATTAACTATCCGCTGGATGACCAGGATGCCATTGCTGTGGAAG CTGCCTGCACTAATGTTCCGGCGTTATTTCTTGATGTCTCTGACCAGACACCCATCAACAGTAT TATTTTCTCCCATGAAGACGGTACGCGACTGGGCGTGGAGCATCTGGTCGCATTGGGTCACCAG CAAATCGCGCTGTTAGCGGGCCCATTAAGTTCTGTCTCGGCGCGTCTGCGTCTGGCTGGCTGGC ATAAATATCTCACTCGCAATCAAATTCAGCCGATAGCGGAACGGGAAGGCGACTGGAGTGCCAT GTCCGGTTTTCAACAAACCATGCAAATGCTGAATGAGGGCATCGTTCCCACTGCGATGCTGGTT GCCAACGATCAGATGGCGCTGGGCGCAATGCGCGCCATTACCGAGTCCGGGCTGCGCGTTGGTG CGGATATCTCGGTAGTGGGATACGACGATACCGAAGACAGCTCATGTTATATCCCGCCGTTAAC CACCATCAAACAGGATTTTCGCCTGCTGGGGCAAACCAGCGTGGACCGCTTGCTGCAACTCTCT CAGGGCCAGGCGGTGAAGGGCAATCAGCTGTTGCCCGTCTCACTGGTGAAAAGAAAAACCACCC TGGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACG AGAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTAAGTTAGCTCACTCA TTAGGCACCGGGATCTCGACCGATGCCCTTGAGAGCGTTCAACCCAGTCAGCTCCTTCCGGTGG GCGCGGGGCATGACTATCGTCGCCGCACTTATGACTGTCTTCTTTATCATGCAACTCGTAGGAC AGGTGCCGGCAGCGCTCTGGGTCATTTTCGGCGAGGACCGCTTTCGCTGGAGCGCGACGATGAT CGGCCTGTCGCTTGCGGTATTCGGAATCTTGCACGCCCTCGCTCAAGCCTTCGTCACTGGTCCC GCCACCAAACGTTTCGGCGAGAAGCAGGCCATTATCGCCGGCATGGCGGCCGACGCGCTGGGCT ACGTCTTGCTGGCGTTCGCGACGCGAGGCTGGATGGCGTTCCCCATTATGATTCTTCTCGCTTC CGGCGGCATCGGGATGCCCGCGTTGCAGGCCATGCTGTCCAGGCAGGTAGATGACGACCATCAG GGACAGCTTCAAGGATCGCTCGCGGCTCTTACCAGCCTAACTTCGATCACTGGACCGCTGATCG TCACGGCGATTTATGCCGCCTCGGCGAGCACATGGAACGGGTTGGCATGGATTGTAGGCGCCGC CCTATACCTTGTCTGCCTCCCCGCGTTGCGTCGCGGTGCATGGAGCCGGGCCACCTCGACCTGA ATGGAAGCCGGCGGCACCTCGCTAACGGATTCACCACTCCAAGAATTGGAGCCAATCAATTCTT GCGGAGAACTGTGAATGCGCAAACCAACCCTTGGCAGAACATATCCATCGCGTCCGCCATCTCC AGCAGCCGCACGCGGCGCATCTCGGGCAGCGTTGGGTCCTGGCCACGGGTGCGCATGATCGTGC TCCTGTCGTTGAGGACCCGGCTAGGCTGGCGGGGTTGCCTTACTGGTTAGCAGAATGAATCACC GATACGCGAGCGAACGTGAAGCGACTGCTGCTGCAAAACGTCTGCGACCTGAGCAACAACATGA ATGGTCTTCGGTTTCCGTGTTTCGTAAAGTCTGGAAACGCGGAAGTCAGCGCCCTGCACCATTA TGTTCCGGATCTGCATCGCAGGATGCTGCTGGCTACCCTGTGGAACACCTACATCTGTATTAAC GAAGCGCTGGCATTGACCCTGAGTGATTTTTCTCTGGTCCCGCCGCATCCATACCGCCAGTTGT TTACCCTCACAACGTTCCAGTAACCGGGCATGTTCATCATCAGTAACCCGTATCGTGAGCATCC TCTCTCGTTTCATCGGTATCATTACCCCCATGAACAGAAATCCCCCTTACACGGAGGCATCAGT GACCAAACAGGAAAAAACCGCGCTTAACATGGCCCGCTTTATCAGAAGCCAGACATTAACGCTT CTGGAGAAACTCAACGAGCTGGACGCGGATGAACAGGCAGACATCTGTGAATCGCTTCACGACC ACGCTGATGAGCTTTACCGCAGCTGCCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACA CATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGT CAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCGCAGCCATGACCCAGTCACGTAGCGATA GCGGAGTGTATACTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATA TGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCTGTTCCGGTTC CTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAG GCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCC AGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCC TGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGA TACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCG GATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTA TCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCC GACCGCTGCGCCTTATCCGGTAAGTATGGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGC CACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTT CTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTG AAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTA GCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCC TTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTC ATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAA TCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTAT CTGAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTGCCCGTCGTGTAGATAACTACG ATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGGGAGACCCACGCTCACCGG CTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAAC TTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTT AATAGTTTGCGCAACGTTGTTGCCATTGCTGCAGGCATCGTGGTGTCACGCTCGTCGTTTGGTA TGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAA AAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCA CTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTG TGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTG CCCGGCGTCAACACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGA AAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAAC CCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAGCAGCGTTTCTGGGTGAGCAAA AACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATA CTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATAT TTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACC TGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCC TTTCGTCTTCAAGAA SEQ ID NO: 34. B1-Kozak-LgBiT-F primer (41 nucleotides) CTGGATCCGCCGCCACCATGGTCTTTCACACTCGAAGATTTC SEQ ID NO: 35. LgBiT-(GS)-R primer (54 nucleotides) ACCGCTCGAGCCTCCACCTCCGCTCCCGCCACCACCGGAACTCCCACTGTTGAT SEQ ID NO: 36. (GS)-YAP50-F primer (69 nucleotides) GGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTGCCGGGCATCAGATCGTGC ACGTC SEQ ID NO: 37. N1-YAP171-Flag-R primer (63 nucleotides) ATGAAACTGCGGCCGCCTTGTCGTCATCGTCTTTGTAGTCTACATCATCAGGTATCTCAAAAG SEQ ID NO: 38. B1-YAP50-F primer (32 nucleotides) CTGGATCCGCCGGGCATCAGATCGTGCACGTC SEQ ID NO: 39. (GS)-YAP171-R primer (68 nucleotides) ACCTGACGACCCTCCACCTCCGCTCCCGCCACCACCGCTCGAGCCTACATCATCAGGTATCTCA AAAG SEQ ID NO: 40. (GS)-LgBiT-F primer (66 nucleotides) GGCTCGAGCGGTGGTGGCGGGAGCGGAGGTGGAGGGTCGTCAGGTGTCTTCACACTCGAAGATT TC SEQ ID NO: 41. N1-LgBiT-R primer (43 nucleotides) ATGAAACTGCGGCCGCTTAACTGTTGATGGTTACTCGGAACAG SEQ ID NO: 42. B1-Kozak-SmiBiT-(GS)-F primer (98 nucleotides) CTGGATCCGCCGCCACCATGGTGACCGGCTACCGGCTGTTCGAGGAGATTCTCGGGAGTTCCGG TGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGT SEQ ID NO: 43. N1-SmBiT-(GS)-R primer (97 nucleotides) ATGAAACTGCGGCCGCTTAGAGAATCTCCTCGAACAGCCGGTAGCCGGTCACACCTGACGACCC TCCACCTCCGCTCCCGCCACCACCGCTCGAGCC SEQ ID NO: 44. (GS)-TEAD-194-F primer (73 nucleotides) GGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTGAGCCTGCATCGGCCCCAG CTCCCTCAG SEQ ID NO: 45. N1-TEAD411-Myc-R primer (73 nucleotides) ATGAAACTGCGGCCGCTTACAGATCCTCTTCTGAGATGAGTTTTTGTTCATTTGAAACTTCAAA CACACAGGC SEQ ID NO: 46. B1-TEAD194-F primer (36 nucleotides) CTGGATCCGAGCCTGCATCGGCCCCAGCTCCCTCAG SEQ ID NO: 47. GS-TEAD-411-R primer (69 nucleotides) ACCTGACGACCCTCCACCTCCGCTCCCGCCACCACCGCTCGAGCCATTTGAAACTTCAAACACA CAGGC SEQ ID NO: 48. (GS)-TEAD194-F primer (73 nucleotides) GGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTGAGCCTGCATCGGCCCCAG CTCCCTGAG SEQ ID NO: 49. TEAD1_HUMAN transcriptional enhancer factor TEF-1 (accession number P28347) mRNA (1,281 nucleotides) ATTGAGCCCAGCAGCTGGAGCGGCAGTGAGAGCCCTGCCGAAAACATGGAAAGGATGAGTGACT CTGCAGATAAGCCAATTGACAATGATGCAGAAGGGGTCTGGAGCCCCGACATCGAGCAAACCTT TCAGGAGGCCCTGGCTATCTATCCACCATGTGGGAGGAGGAAAATCATCTTATCAGACGAAGGC AAAATGTATGGTAGGAATGAATTGATAGCCAGATACATCAAACTCAGGACAGGCAAGACGAGGA CCAGAAAACAGGTGTCTAGTCACATTCAGGTTCTTGCCAGAAGGAAATCTCGTGATTTTCATTC CAAGCTAAAGGATCAGACTGCAAAGGATAAGGCCCTGCAGCACATGGCGGCCATGTCCTCAGCC CAGATCGTCTCGGCCACTGCGATTCATAAGAAGCTGGGGCTGCCTGGGATTCCACGCCCGACCT TCCCAGGGGCGCCGGGGTTCTGGCCGGGAATGATTCAAACAGGGCAGCCAGGATCCTCACAAGA CGTCAAGCCTTTTGTGCAGCAGGCCTACCCCATCCAGCCAGCGGTCACAGCCCCCATTCCAGGG TTTGAGCCTGCATCGGCCCCAGCTCCCTCAGTCCCTGCCTGGCAAGGTCGCTCCATTGGCACAA CCAAGCTTCGCCTGGTGGAATTTTCAGCTTTTCTCGAGCAGCAGCGAGACCCAGACTCGTACAA CAAACACCTCTTCGTGCACATTGGGCATGCCAACCATTCTTACAGTGACCCATTGCTTGAATCA GTGGACATTCGTCAGATTTATGACAAATTTCCTGAAAAGAAAGGTGGCTTAAAGGAACTGTTTG GAAAGGGCCCTCAAAATGCCTTCTTCCTCGTAAAATTCTGGGCTGATTTAAACTGCAATATTCA AGATGATGGTGGGGCTTTTTATGGTGTAACCAGTCAGTACGAGAGTTCTGAAAATATGACAGTC ACCTGTTCCACCAAAGTTTGCTCCTTTGGGAAGCAAGTAGTAGAAAAAGTAGAGACGGAGTATG CAAGGTTTGAGAATGGCCGATTTGTATACCGAATAAACCGCTCCCCAATGTGTGAATATATGAT CAACTTCATCCACAAGCTCAAACACTTACCAGAGAAATATATGATGAACAGTGTTTTGGAAAAC TTCACAATTTTATTGGTGGTAACAAACAGGGATACACAAGAAACTCTACTCTGCATGGCCTGTG TGTTTGAAGTTTCAAATAGTGAACACGGAGCACAACATCATATTTACAGGCTTGTAAAGGACTG A SEQ ID NO: 50. TEAD1_HUMAN protein (426 amino acids) MEPSSWSGSESPAENMERMSDSADKPIDNDAEGVWSPDIEQSFQEALAIYPPCGRRKIILSDEG KMYGRNELIARYTKLRTGKTRTRKQVSSHIQVLARRKSRDFHSKLKDQTAKDKALQHMAAMSSA QIVSATAIHNKLGLPGIPRPTFPGAPGFWPGMIQTGQPGSSQDVKPFVQQAYPIQPAVTAPIPG FEPASAPAPSVPAWQGRSIGTTKLRLVEFSAFLEQQRDPDSYNKHLFVHIGHANHSYSDPLLES VDIRQIYDKFPEKKGGLKELFGKGPQNAFFLVKFWADLNCNIQDDAGAFYGVTSQYESSENMTV TCSTKVCSFGKQVVEKVETEYARFENGRFVYRINRSPMCEYMINFIHKLKHLPEKYMMNSVLEN FTILLVVTNRDTQETLLCMACVFEVSNSEHGAQHHIYRLVKD SEQ ID NO: 51. Large BiT (LgBiT) mRNA (477 nucleotides) ATGGTCTTCACACTCGAAGATTTCGTTGGGGACTGGGAACAGACAGCCGCCTACAACCTGGACC AAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGCTGCAGAATCTCGCCGTGTCCGTAACTCCGAT CCAAAGGATTGTCCGGAGCGGTGAAAATGCCCTGAAGATCGACATCCATGTCATCATCCCGTAT GAAGGTCTGAGCGCCGACCAAATGGCCCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGG ATGATCATCACTTTAAGGTGATCCTGCCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAA CATGCTGAACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACT GTAACAGGGACCCTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCT CCATGCTGTTCCGAGTAACCATCAACAGT SEQ ID NO: 52. Large BiT (LgBiT) protein (159 amino acids) MVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPY EGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYSGIAVFDGKKIT VTGTLWNGNKIIDERLITPDGSMLFRVTINS SEQ ID NO: 53. Small BiT (SmBiT) mRNA (36 nucleotides) ATGGTGACCGGCTACCGGCTGTTCGAGGAGATTCTC SEQ ID NO: 54. Small BiT (SmBiT) protein (11 amino acids) MVTGYRLFEIL SEQ ID NO: 55. pcDNA3.1/hygro(+)-Flag vector (5,490 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGCG TTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTAT TAATAGTAATGAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAAC TTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGAC GTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGG TAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCA ATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTG GCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAAT GGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGA GTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGAC GCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGA GAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCT AGCGTTTAAACTTAAGCTTGGTACCATGGACTACAAAGACGATGACGGTGATTATAAAGATCAT GACATCTACCTGATGTTTCTGGTACTGCCAGGATCCACTAGTCCAGTGTGGTGGAATTCTGCAG ATATCCAGGACAGTGGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCG ACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGG AAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAG GTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAAT AGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCT CTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCG CAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTT CTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGGTCCCTTTAGGGTTCCGAT TTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCC ATCGCCCTGATAGACGGTTTTTCGCCGTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTC TTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTT TGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATT CTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGC AAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAG AAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATC CCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTT ATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGG AGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAG ACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTT GGGTGGAGAGGCTATTCGGCTATGACTGGGCAGAACAGACAATCGGCTGCTCTGATGCCGCCGT GTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTG AATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAG CTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCA GGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGG CGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGC GAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGG GCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTC GTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCA TCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATAT TGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCC GATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTT CGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTC TATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGG ATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATA AAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTG TCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGT AATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACG AGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCG TTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCC AACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCT GCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCC ACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACC GTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAA TCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCT GGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTC CGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCC GGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTG GTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAA CTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGA AAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCA AGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTC TGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATC TTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAA CTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCT GGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAA ACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTC TATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTT GCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTT CCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGG TCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTG CATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCA AGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAA TACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAA CTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGAT CTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGC AAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTAT TGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATA AACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC  SEQ ID NO: 56 pcDNA3.1/hygro(+)-Myc vector (5,455 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCATGGAACAAAAACTCATCTCAGAAGAGGATCTGGGATC CACTAGTCCAGTGTGGTGGAATTCTGCAGATATCCAGCACAGTGGCGGCCGCTCGAGTCTAGAG GGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCGAGCCATCTGTTGTTTG CCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAAT GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGG ACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGC TTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCA TTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGC CCGCTCCTTTGGCTTTCTTCCCTTGCTTTCTCGCGACGTTCGCCGGCTTTCCCCGTCAAGCTCT AAATCGGGGGCTCGCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTT GATTAGGGTGATGGTTGACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGT TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTC GGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTG ATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTC CCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGT GGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAA CCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCC GCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTA TTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTT GTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAAGAAGA TGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAA CAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGGGCAGGGGCGCCCGGTTCTTT TTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTG GCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGAC TGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGA AAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATT CGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGAT CAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGG CGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCAT GGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTAT CAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCT TCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGA CGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGCGACGCCCAACCTGCCAT CACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGA CGCCGGCTGGATGATCCTGCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTG TTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCAT TTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAT ACCGTCGACGTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTGCTGTGTGAAATTGT TATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCT AATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCT GTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGC TCTTCCGGTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGGGAGCGGTATCAG CTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTG AGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGG CTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAG GACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCT GCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCA CGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCC CCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACA CGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGT GCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCT GCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAAC CACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAA GAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGA TTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTT TAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAG GCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGA TAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACG CTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGT CCTGCAACTTTATCCGCCTCGATCCAGTCTATTAATTGTTGCGGGGAAGCTAGAGTAAGTAGTT CGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTC GTTTGGTATGGCTTCATTCAGCTCCGGTTCCGAACGATCAAGGCGAGTTACATGATCCCCCATG TTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAG TGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTAGTGTCATGCCATCCGTAAGATG CTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGT TGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCA TCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTC GATGTAACCCACTCGTGCACCCAACTGATGTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGG TGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAA TACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGG ATACATATTTGAATGTATTTAGAAABATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAA GTGCCACCTGACGTC SEQ ID NO: 57. Intermolecular biosensor Nluc-YAP15 in pcDNA3.1/ hygro(+) vector (6,693 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGGGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGAAGACGCCAAAAACATAAAGAA AGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACCGCTGGAGAGCAACTGCATAAGGCTATG AAGAGATACGCCCTGGTTCCTGGAACAATTGCTTTTACAGATGCACATATCGAGGTGGACATCA CTTACGCTGAGTACTTCGAAATGTCCGTTCGGTTGGCAGAAGCTATGAAACGATATGGGCTGAA TACAAATCACAGAATCGTCGTATGCAGTGAAAACTCTCTTCAATTCTTTATGCCGGTGTTGGGC GCGTTATTTATCGGAGTTGCAGTTGCGCCCGCGAACGACATTTATAATGAACGTGAATTGCTCA ACAGTATGGGCATTTCGCAGCCTACCGTGGT G TTCGTTTCCAAAAAGGGGTTGCGAAAAATTTT GAACGTGCAAAAAAAGCTCCCAATCATCCAAAAAATTATTATCATGGATTCTAAAACGGATTAC CAGGGATTTCAGTCGATGTACACGTTCGTCACATCTCATCTACCTCCCGGTTTTAATGAATACG ATTTTGTGCCAGAGTCCTTCGATAGGGACAAGACAATTGCACTGGTCATGAACTCCTCTGGATC TACTGGTCTGCCTAAAGGTGTCGCTCTGCCTCATAGAACTGCCTGCGTGAGATTCTCGCATGCC AGAGATCCTATTTTTGGCAATCAAATCATTCCGGATACTGCGATTTTAAGTGTTGTTCCATTCC ATCACGGTTTTGGAATGTTTACTACACTCGGATATTTGATATGTGGATTTCGAGTCGTCTTAAT GTATAGATTTGAAGAAGAGCTGTTTCTGAGGAGCCTTCAGGATTACAAGATTCAAAGTGCGCTG CTGGTGCCAACCCTATTCTCCTTCTTCGCCAAAAGCACTCTGATTGACAAATACGATTTATCTA ATTTACACGAAATTGCTTCTGGTGGCGCTCCCCTCTCTAAGGAAGTCGGGGAAGCGGTTGCCAA GAGGTTCCATCTGCCAGGTATCAGGCAAGGATATGGGCTCACTGAGACTACATCAGCTATTCTG ATTACACCCGAGGGGGATGATAAACCGGGCGCGGTCGGTAAAGTTGTTCCATTTTTTGAAGCGA AGGTTGTGGATCTGGATACCGGGAAAACGCTGGGCGTTAATCAAAGAGGCGAACTGTGTGTGAG AGGTCCTATGATTATGTCCGGTTATGTAAACAATCCGGAAGCGACCAACGCCTTGATTGACAAG GATGGAGGAGGAGCTGGAGGCCCACAGCATGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGT TG GCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTA GTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCC CACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATT CTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTG GGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCC CCACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCT ACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCG CCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACG GCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAG ACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTG GAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGC CTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGT GTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCT CAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGC ATGCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTC CGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGA GGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTT TGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGAT CGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCT ATTCGGCTATGACTGGGCACAACAGAGAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCA GCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAGG ACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGT TGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCA TCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGC TTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCG GATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCC GAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCG ATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCG GCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTT GGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCA TCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGAC CAAGGGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGG GCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGA GTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATC ACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCA ATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATA GCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATA AAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGC CCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAG AGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTT CGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGG ATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGC GTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGT CAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCG TGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCGGCCTTTCTCCCTTCGGGAAG CGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAG CTGGGCTGTGTGCACGAACCGCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTC TTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAG CAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACT AGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTA GCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTAC GCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTGTGACGCTCAGTGG AACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCC TTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAG TTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTT GCCTGACTCCCCGTCGTGTAGATAACTAGGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTG CAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGG AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGC CGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCGATTGCTACAG GCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAG GCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTT GTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTA CTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGA ATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCGACAT AGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCT TACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTT TACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATA AGGGCGACACGGAAATGTTGAATACTCATACTCTTCGTTTTTCAATATTATTGAAGCATTTATC AGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGT TCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 58. Intermolecular biosensor 14-3-3-Cluc in pcDNA3.1/ hygro(+) vector (6,621 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGACTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGGCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGAGAAGACTGAGCTGATCCAGAA GGCCAAGCTGGCCGAGCAGGCCGAGCGCTACGACGACATGGCCACCTGCATGAAGGCAGTGACC GAGCAGGGGGCCGAGCTGTCCAACGAGGAGCGCAACCTGCTCTCCGTGGCCTACAAGAACGTGG TCGGGGGCCGCAGGTCCGCCTGGAGGGTCATCTCTAGCATCGAGCAGAAGACCGACACCTCCGA CAAGAAGTTGCAGCTGATTAAGGACTATCGGGAGAAAGTGGAGTCCGAGCTGAGATCCATCTGC ACCACGGTGCTGGAATTGTTGGATAAATATTTAATAGCCAATGCAACTAATCCAGAGAGTAAGG TCTTCTATCTGAAAATGAAGGGTGATTACTTCCGGTACCTTGCTGAAGTTGCGTGTGGTGATGA TCGAAAACAAACGATAGATAATTCCCAAGGAGCTTACCAAGAGGCATTTGATATAAGCAAGAAA GAGATGCAACCCACACACCCAATCCGCCTGGGGCTTGCTCTTAACTTTTCTGTATTTTACTATG AGATTCTTAATAACCCAGAGCTTGCCTGCACGCTGGCTAAAACGGCTTTTGATGAGGCCATTGC TGAACTTGATACACTGAATGAAGACTCATACAAAGACAGCACCCTCATCATGCAGTTGCTTAGA GACAACCTAACACTTTGGACATCAGACAGTGCAGGAGAAGAATGTGATGCGGCAGAAGGGGCTG AAAACGGAGGAGGAGGTAGTGGAGGAGGAGGTAGTCCTATGATTATGTCCGGTTATGTAAACAA TCCGGAAGCGACCAACGCCTTGATTGACAAGGATGGATGGCTACATTCTGGAGACATAGCTTAC TGGGACGAAGACGAACACTTCTTCATCGTTGACCGCCTGAAGTCTCTGATTAAGTACAAAGGCT ATCAGGTGGCTCCCGCTGAATTGGAATCCATCTTGCTCCAACACCCCAACATCTTCGACGCAGG TGTCGCAGGTCTTCCCGACGATGACGCCGGTGAACTTCCCGCCGCCGTTGTTGTTTTGGAGCAC GGAAAGACGATGACGGAAAGAGAGATCGTGGATTACGTCGCCAGTCAAGTAACAACCGCGGAAA AGTTGCGCGGAGGAGTTGTGTTTGTGGACGAAGTACCGAAAGGTCTTACCGGAAAACTCGACGC AAGAAAAATCAGAGAGATCCTCATAAAGGCCAAGAAGGGCGGAAAGATCGCCGTGTAA GCGGCC GCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAG CCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCC TTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGG TGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGGG GTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGCGC CCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGC CAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTT CCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCG ACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTT TCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACA CTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGT TAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAGTTA GGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGT CAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCT CAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGT TCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCT CTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAA GCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTCGC ATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCT ATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGG GCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAGGACGAGGCA GCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTG AAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCT TGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCG GCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAG CCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTT CGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGC TTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTG TGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGA ATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTC TATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGCGAC GCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGA ATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCG CCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTT CACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCT TATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGGGTAATCATGGTCATAGCTGTTTC CTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAA AGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTC CAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTT TGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCG GCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCA GGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGG CGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTG GCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCT CCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGC TTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTG TGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCC AACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGA GGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAAC AGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGA TCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAA AAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAA CTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAAT TAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAAT GCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACT CCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATA CCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCG AGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGC TAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTG GTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTA CATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATG CCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTA TGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAAC TTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTG TTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCA CCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGAC ACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTAT TGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCA CATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 59. NanoBiT Biosensor: LgBiT-YAP15 in pBiT 1.1 N vector (3,890 nucleotides) GGCCTAACTGGCCGGTACCTGAGTCTAAATGAGTCTTCGGACCTCGCGGGGGCCGCTTAAGCGG TGGTTAGGGTTTGTCTGACGCGGGGGGAGGGGGAAGGAACGAAACACTCTCATTCGGAGGCGGC TCGGGGTTTGGTGTTGGTGGCCACGGGCACGCAGAAGAGCGCCGCGATCCTCTTAAGCACCCCC CCGCCCTCCGTGGAGGCGGGGGTTTGGTCGGCGGGTGGTAACTGGCGGGCCGCTGACTCGGGCG GGTCGCGCGCCCCAGAGTGTGACCTTTTCGGTCTGCTCGCAACCCCCGGGCGGCGCCGCCGCGG CGGCGACGGGCTCGCTGGGTCCTAGGCTCCATGGGGACCGTATACGTGGACAGGCTCTGGAGCA TCCGCACGACTGCGGTGATATTACCGGAGACCTTCTGCGGGACGAGCCGGGTCACGCGGCTGAC CCGGAGCGTCCGTTGGGCGACAAACACCAGGACGGGGCACAGGTACACTATCTTGTCACCCGGA GGCGCGAGGGACTGCAGGAGCTTGAGGGAGTGGCGCAGCTGCTTCATCCCCGTGGCCCGTTGCT CGCGTTTGCTGGCGGTGTCCCCGGAAGAAATATATTTGCATGTCTTTAGTTCTATGATGACACA AACCCCGCCCAGCGTCTTGTCATTGGCGAAGTCGAACACGCAGATGCAGTCGGGGCGGCGCGGT CCCAGGTCCACTTCGCATATTAAGGTGACGCGTGTGGCCTCGAACACCGAGCGACCCTGCAGCG ACCCGCTTAAAAGCTTGGCAATCCGGTACTGTTGGTAAAGCCACC ATGGTCTTCACACTCGAAG ATTTCGTTGGGGACTGGGAACAGACAGCCGCCTACAACCTGGACCGAGTCCTTGAACAGGGAGG TGTGTCCAGTTTGCTGCAGAATCTCGCCGTGTCCGTAACTCCGATCCAAAGGATTGTCCGGAGC GGTGAAAATGCCCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGGGCGCCGACC AAATGGCCCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGT GATCCTGCCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGCTGAACTATTTCGGA CGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGA ACGGCAACAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCTCCATGCTGTTCCGAGTAAC CATCAACAGTGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTGGAGCTCAG GGGAATTCCCCACAGCATGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGTTG AGATCTTCTA GAGTCGGGGCGGCCGGCCGCTTCGAGCAGACATGATAAGATACATTGATGAGTTTGGACAAACC ACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTG TAACCATTATAAGCTGCAATAAACAAGTTAACAACAACAATTGCATTCATTTTATGTTTCAGGT TCAGGGGGAGGTGTGGGAGGTTTTTTAAAGCAAGTAAAACCTCTACAAATCTGGTAAAATCGAT AAGGATCCGTCGACCGATGCCCTTGAGAGCCTTCAACCCAGTCAGCTCCTTCCGGTGGGCGCGG GGCATGACTATCGTCGCCGCACTTATGACTGTCTTCTTTATCATGCAACTCGTAGGACAGGTGC CGGCAGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAG CGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAA GAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTT TTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAA ACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGT TCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCT CATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTGGTTCGCTCCAAGCTGGGCTGTGTGC ACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCC GGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTAT GTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTAT TTGGTATCTGCGGTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGG CAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAA AAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACT CACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTA AAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGCGGCCGCAAA TGCTAAACCACTGCAGTGGTTACCAGTGCTTGATCAGTGAGGCACCGATCTCAGCGATCTGCCT ATTTCGTTCGTCCATAGTGGCCTGACTCCCCGTCGTGTAGATCACTACGATTCGTGAGGGCTTA CCATCAGGCCCCAGCGCAGCAATGATGCCGCGAGAGCCGCGTTCACCGGCCCCCGATTTGTCAG CAATGAACCAGCCAGCAGGGAGGGCCGAGCGAAGAAGTGGTCCTGCTACTTTGTCCGCCTCCAT CCAGTCTATGAGCTGCTGTCGTGATGCTAGAGTAAGAAGTTCGCCAGTGAGTAGTTTCCGAAGA GTTGTGGCCATTGCTACTGGCATCGTGGTATCACGCTCGTCGTTCGGTATGGCTTCGTTCAACT CTGGTTCCCAGCGGTCAAGCCGGGTCACATGATCACCCATATTATGAAGAAATGCAGTCAGCTC CTTAGGGCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCGGTGTTGTCGCTCATGGTAATGGCA GCACTACACAATTCTCTTACCGTCATGCCATCCGTAAGATGCTTTTCCGTGACCGGCGAGTACT CAACCAAGTCGTTTTGTGAGTAGTGTATACGGCGACCAAGCTGCTCTTGCCCGGCGTCTATACG GGACAACACCGCGCCACATAGCAGTACTTTGAAAGTGCTCATCATCGGGAATCGTTCTTCGGGG CGGAAAGACTCAAGGATCTTGCCGCTATTGAGATCCAGTTCGATATAGCCCACTCTTGCACCCA GTTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCGGGGTGTGCAAAAACAGGCAAGCAAAA TGCCGCAAAGAAGGGAATGAGTGCGACACGAAAATGTTGGATGCTCATACTCGTCCTTTTTCAA TATTATTGAAGCATTTATCAGGGTTACTAGTACGTCTCTCAAGGATAAGTAAGTAATATTAAGG TACGGGAGGTATTGGACAGGCCGCAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTT TTTTGTGTGAATCGATAGTACTAACATACGCTCTCCATCAAAACAAAACGAAACAAAACAAACT AGCAAAATAGGCTGTCCCCAGTGCAAGTGCAGGTGCCAGAACATTTCTCT SEQ ID NO: 60. NanoBiT Biosensor: 14-3-3-LgBiT in pBiT2.1-C vector (4,131 nucleotides) GGCCTAACTGGCCGGTACCTGAGTCTAAATGAGTCTTCGGACCTCGCGGGGGCCGCTTAAGCGG TGGTTAGGGTTTGTCTGACGCGGGGGGAGGGGGAAGGAACGAAACACTCTCATTCGGAGGCGGC TCGGGGTTTGGTCTTGGTGGCCACGGGCACGCAGAAGAGCGCCGCGATCCTCTTAAGCACCCCC CCGCCCTCCGTGGAGGCGGGGGTTTGGTCGGCGGGTGGTAACTGGCGGGCCGCTGACTCGGGCG GGTCGCGCGCCCCAGAGTGTGACCTTTTCGGTCTGCTCGCAGACCCCCGGGCGGCGCCGCCGCG GCGGCGACGGGCTCGCTGGGTCCTAGGCTCCATGGGGACCGTATACGTGGACAGGCTCTGGAGC ATCCGCACGACTGCGGTGATATTACCGGAGACCTTCTGCGGGACGAGCCGGGTCACGCGGCTGA CGCGGAGCGTCCGTTGGGCGACAAACACCAGGACGGGGCACAGGTACACTATCTTGTCACCCGG AGGCGCGAGGGACTGCAGGAGCTTCAGGGAGTGGCGCAGCTGCTTCATCCCCGTGGCCCGTTGC TCGCGTTTGCTGGCGGTGTCCCCGGAAGAAATATATTTGCATGTCTTTAGTTCTATGATGACAC AAACCCCGCCCAGCGTCTTGTCATTGGCGAAGTCGAACACGCAGATGCAGTCGGGGCGGCGCGG TCCCAGGTCCACTTCGCATATTAAGGTGACGCGTGTGGCCTCGAACACCGAGCGACCCTGCAGC GACCCGCTTAAAAGCTTGGCAATCCGGTACTGTGGTAAAGCCACCAGATCTA ATGGAGAAGACT GAGCTGATCCAGAAGGCCAAGCTGGCCGAGCAGGCCGAGCGCTACGACGACATGGCCACCTGCA TGAAGGCAGTGACCGAGCAGGGCGCCGAGCTGTCCAACGAGGAGCGCAACCTGCTCTCCGTGGC CTACAAGAACGTGGTCGGGGGCCGCAGGTCCGCCTGGAGGGTCATCTCTAGCATCGAGCAGAAG ACCGACACCTCCGACAAGAAGTTGCAGCTGATTAAGGACTATCGGGAGAAAGTGGAGTCCGAGC TGAGATCCATCTGCACCACGGTGCTGGAATTGTTGGATAAATATTTAATAGCCAATGCAACTAA TCCAGAGAGTAAGGTCTTCTATCTGAAAATGAAGGGTGATTACTTCCGGTACCTTGCTGAAGTT GCGTGTGGTGATGATCGAAAACAAACGATAGATAATTCCCAAGGAGCTTACCAAGAGGCATTTG ATATAAGCAAGAAAGAGATGCAACCCACACACCCAATCCGCCTGGGGCTTGCTCTTAACTTTTC TGTATTTTACTATGAGATTCTTAATAACCCAGAGCTTGCCTGCACGCTGGCTAAAACGGCTTTT GATGAGGCCATTGCTGAACTTGATACACTGAATGAAGACTCATACAAAGACAGCACCCTCATCA TGCAGTTGCTTAGAGACAACCTAACACTTTGGACATCAGACAGTGCAGGAGAAGAATGTGATGC GGCAGAAGGGGCTGAAAACCCGAATTCTGGCTCGAGCGGTGGTGGCGGGAGCGGAGGTGGAGGG TCGTCAGGTGTGACCGGCTACCGGCTGTTCGAGGAGATTCTGTAA TCTAGAGTCGGGGCGGCCG GCCGCTTCGAGCAGACATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAG TGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCT GCAATAAACAAGTTAACAACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTG GGAGGTTTTTTAAAGCAAGTAAAACCTCTACAAATGTGGTAAAATCGATAAGGATCCGTCGACC GATGCCCTTGAGAGCCTTCAACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTC GCCGCACTTATGACTGTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTTCC GCTTCCTCGCTGACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACT CAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAA AGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGC CCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTAT AAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCT TACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGT AGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTC AGCCCGAGCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTT ATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACA GAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTC TGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGC TGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAA GATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTT TGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAA ATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGCGGCCGCAAATGCTAAACCACTGCA GTGGTTACCAGTGCTTGATCAGTGAGGCACCGATCTCAGCGATCTGCCTATTTCGTTCGTCCAT AGTGGCCTGACTCCCCGTCGTGTAGATCACTACGATTCGTGAGGGCTTACCATCAGGCCCCAGC GCAGCAATGATGCCGCGAGAGCCGCGTTCACCGGCCCCCGATTTGTCAGCAATGAACCAGCCAG CAGGGAGGGCCGAGCGAAGAAGTGGTCCTGCTACTTTGTCCGCCTCCATCCAGTCTATGAGCTG CTGTCGTGATGCTAGAGTAAGAAGTTCGCCAGTGAGTAGTTTCCGAAGAGTTGTGGCCATTGCT ACTGGCATCGTGGTATCACGCTCGTCGTTCGGTATGGCTTCGTTCAACTCTGGTTCCCAGCGGT CAAGCCGGGTCACATGATCACCCATATTATGAAGAAATGCAGTCAGCTCCTTAGGGCCTCCGAT CGTTGTCAGAAGTAAGTTGGCCGCGGTGTTGTCGCTCATGGTAATGGCAGCACTACACAATTCT CTTACCGTCATGCCATCCGTAAGATGCTTTTCCGTGACCGGCGAGTACTCAACCAAGTCGTTTT GTGAGTAGTGTATACGGCGACCAAGCTGCTCTTGCCCGGCGTCTATACGGGACAACACCGCGCC ACATAGCAGTACTTTGAAAGTGCTCATCATCGGGAATCGTTCTTCGGGGCGGAAAGACTCAAGG ATCTTGCCGCTATTGAGATCCAGTTCGATATAGCCCACTCTTGCACCCAGTTGATCTTCAGCAT CTTTTACTTTCACCAGCGTTTCGGGGTGTGCAAAAACAGGCAAGCAAAATGCCGCAAAGAAGGG AATGAGTGCGACACGAAAATGTTGGATGCTCATACTCGTCCTTTTTCAATATTATTGAAGCATT TATCAGGGTTACTAGTACGTCTCTCAAGGATAAGTAAGTAATATTAAGGTACGGGAGGTATTGG ACAGGCCGCAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGAATCGA TAGTACTAACATACGCTCTCCATCAAAACAAAACGAAACAAAACAAACTAGCAAAATAGGCTGT CCCCAGTGCAAGTGCAGGTGCCAGAACATTTCTCT SEQ ID NO: 61. NanoBiT Biosensor: LgBiT-YAP15 in pET16b vector  (6,291 nucleotides) TTCTTGAAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATG GTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTT TCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATA TTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCA TTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCG CCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCC CGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTG AGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGC TGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAG GAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGG AGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAAC GTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGG ATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTG CTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGG TAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAAT AGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACT CATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCT TTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCC GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAA CAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC GAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTA GGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACGTCGCTCTGCTAATCCTGTTACCAG TGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGA TAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACC TACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGG GGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGT TCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGA TAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGC GAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCG GTATTTCACACCGCATATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGC CAGTATACACTCCGCTATCGCTACGTGACTGGGTCATGGCTGCGCCCCGACACCCGGCAACACC CGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTC TCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGGCAGCTGCGGT AAAGCTCATCAGCGTGGTCGTGAAGCGATTCACAGATGTCTGCCTGTTCATCCGCGTCCAGCTC GTTGAGTTTCTCCAGAAGCGTTAATGTCTGGCTTCTGATAAAGCGGGCCATGTTAAGGGCGGTT TTTTCCTGTTTGGTCACTGATGCCTCCGTGTAAGGGGGATTTCTGTTCATGGGGGTAATGATAC CGATGAAACGAGAGAGGATGCTCACGATACGGGTTACTGATGATGAACATGCCCGGTTACTGGA ACGTTGTGAGGGTAAACAACTGGCGGTATGGATGCGGCGGGACCAGAGAAAAATCACTCAGGGT CAATGCCAGCGCTTCGTTAATACAGATGTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCGA TGCAGATCCGGAACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACACG GAAACCGAAGACCATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTTCAC GTTCGCTCGCGTATCGGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCTAGCCGGG TCCTCAACGACAGGAGCACGATCATGCGCACCCGTGGCCAGGACCCAACGCTGCCCGAGATGCG CCGCGTGCGGCTGCTGGAGATGGCGGACGCGATGGATATGTTCTGCCAAGGGTTGGTTTGCGCA TTCACAGTTCTCCGCAAGAATTGATTGGCTCCAATTCTTGGAGTGGTGAATCCGTTAGCGAGGT GCCGCCGGCTTCCATTCAGGTCGAGGTGGCCCGGCTCCATGCACCGCGACGCAACGCGGGGAGG CAGACAAGGTATAGGGCGGCGCCTACAATCCATGCCAACCCGTTCCATGTGCTCGCCGAGGCGG CATAAATCGCCGTGACGATCAGCGGTCCAGTGATCGAAGTTAGGCTGGTAAGAGCCGCGAGCGA TCCTTGAAGCTGTCCCTGATGGTCGTCATCTACCTGCCTGGACAGCATGGCCTGCAACGCGGGC ATCCCGATGCCGCCGGAAGCGAGAAGAATCATAATGGGGAAGGCCATCCAGCCTCGCGTCGCGA ACGCCAGCAAGACGTAGCCCAGCGCGTCGGCCGCCATGCCGGCGATAATGGCCTGCTTCTCGCC GAAACGTTTGGTGGCGGGACCAGTGACGAAGGCTTGAGCGAGGGCGTGCAAGATTCCGAATACC GCAAGCGACAGGCCGATCATCGTCGCGCTCCAGCGAAAGCGGTCCTCGCCGAAAATGACCCAGA GCGCTGCCGGCACCTGTCCTACGAGTTGCATGATAAAGAAGACAGTCATAAGTGCGGCGACGAT AGTCATGCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGAAGGCTCTCAAGGGCATCGGTCGA GATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCGTTGCGCTCACTGCCCGCTTTCC AGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTT GCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCAACAGCTGATTGCCCTT CACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCCCCAGCAGGCGAAAA TCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGTATCGTCGTATCCCA CTACCGAGATATCCGCACCAACGCGCAGCCCGGACTCGGTAATGGCGCGCATTGCGCCCAGCGC CATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGCATGGTT TGTTGAAAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGC GAGTGAGATATTTATGCCAGCCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGGGCCCGC TAACAGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTACCGTCT TCATGGGAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCGGAA CATTAGTGCAGGCAGCTTCCACAGCAATGGCATCCTGGTCATCCAGCGGATAGTTAATGATCAG CCCACTGACGCGTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGT TCTACCATCGACACCACCACGCTGGCACCCACTTGATCGGCGCGAGATTTAATCGCCGCCACAA TTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCAACGCCAATCAGCAACGACTGTTTGCC CGCCAGTTGTTGTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCACTTTT TCCCGCGTTTTCGCAGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGA CACCGGCATACTCTGCGACATCGTATAACGTTACTGGTTTGACATTCACCACCCTGAATTGACT CTCTTCCGGGCGCTATCATGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATC TCGACGCTCTCCCTTATGCGACTCCTGCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTG AGCACCGCCGCCGCAAGGAATGGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCACGG GGCCTGCCACCATACCCACGCCGAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTC CCCATCGGTGATGTCGGCGATATAGGCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCC ACGATGCGTCCGGCGTAGAGGATCGAGATCTCGATCCCGCGAAATTAATACGACTCACTATAGG GGAATTGTGAGCGGATAACAATTCCCCTCTAGAAATAATTTTGTTTAACTTTAAGAAGGAGATA TACCATGGGCCATCATCATCATCATCATCATGATCATCACAGCAGCGGCCATATCGAAGGTCGT CATATG ATGGTCTTCACACTCGAAGATTTCGTTGGGGACTGGGAACAGACAGCCGCCTACAACC TGGACCAAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGCTGCAGAATCTCGCCGTGTCCGTAAC TCCGATCCAAAGGATTGTCCGGAGCGGTGAAAATGCCCTGAAGATCGACATCCATGTCATCATC CCGTATGAAGGTCTGAGCGCCGACCAAATGGCCCAGATCGAAGAGGTGTTTAAGGTGGTGTACC CTGTGGATGATCATCACTTTAAGGTGATCCTGCCCTATGGCACACTGGTAATCGACGGGGTTAC GCCGAACATGCTGAACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAG ATCACTGTAACAGGGACCCTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCACCCCCG ACGGCTCCATGCTGTTCCGAGTAACCATCAGCAGTGGGAGTTCCGGTGGTGGCGGGAGCGGAGG TGGAGGCTCGAGCGGTGGAGCTCAGGGGAATTCCCCACAGCATGTTCGAGCTCATTCCTCTCCA GCTTCTCTGCAGTTG GGATCCGGCTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTCCTGCC ACCGGTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAAGGGGTCTTGAGGGGTTTTTTGC TGAAAGGAGGAACTATATCCGGATATCCCGCAAGAGGCCCGGCAGTACCGGCATAACCAAGCCT ATGCCTACAGCATCCAGGGTGACGGTGCTGAGGATGACGATGAGCGCATTGTTAGATTTCATAC ACGGTGCCTGACTGCGTTAGCAATTTAACTGTGATAAACTACCGCATTAAAGCTTATCGATGAT AAGCTGTCAAACATGAGAA SEQ ID NO: 62. NanoBiT Biosensor: SmBiT in pET16b vector  (6,531 nucleotides) TTCTTGAAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATG GTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTT TCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATA TTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCA TTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCG CCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCC CGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTG AGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGC TGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTGTGACAACGATCGGAGGACCGAAG GAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGG AGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAAC GTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGG ATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTG CTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGG TAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAAT AGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACT CATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCT TTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCC GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAA CAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC GAAGGTAACTGGCTTCAGCAGAGCGCAGATACGAAATACTGTCCTaCTAGTGTAGCCGTAGTTA GGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAG TGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGA TAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACG TACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGG GGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGT TCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGA TAACCGTATTACCGGCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGC GAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCG GTATTTCACACCGCATATATGGTGCACTCTCAGTACAATGTGCTCTGATGCCGCATAGTTAAGC CAGTATACACTCCGCTATCGCTACGTGACTGGGTCATGGCTGCGCCCCGACACCCGCCAAGACC CGCTGACGCGCCCTGACGGGCTTGTGTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTC TCCGGGAGCTGCATGTGTGAGAGGTTTTCACGGTGATCACCGAAACGCGCGAGGCAGCTGCGGT AAAGCTCATCAGCGTGGTCGTGAAGCGATTCACAGATGTCTGCCTGTTCATCCGCGTCCAGCTC GTTGAGTTTCTCCAGAAGCGTTAATGTCTGGCTTCTGATAAAGCGGGCCATGTTAAGGGCGGTT TTTTCCTGTTTGGTCACTGATGCCTCCGTGTAAGGGGGATTTCTGTTGATGGGGGTAATGATAC CGATGAAACGAGAGAGGATGCTCACGATACGGGTTACTGATGATGAACATGCCCGGTTACTGGA ACGTTGTGAGGGTAAACAACTGGCGGTATGGATGCGGCGGGACCAGAGAAAAATCACTCAGGGT CAATGCCAGCGCTTCGTTAATACAGATGTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCGA TGCAGATCCGGAACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACACG GAAACCGAAGACCATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTTCAC GTTCGCTCGCGTATCGGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCTAGCCGGG TCCTCAACGACAGGAGCACGATCATGCGCACCCGTGGCCAGGACCCAACGCTGCCCGAGATGCG CCGCGTGCGGCTGCTGGAGATGGCGGACGCGATGGATATGTTCTGCCAAGGGTTGGTTTGCGCA TTCACAGTTCTCCGCAAGAATTGATTGGCTCCAATTCTTGGAGTGGTGAATCCGTTAGCGAGGT GCCGCCGGCTTCCATTCAGGTCGAGGTGGCCCGGCTCCATGCACCGCGACGCAACGCGGGGAGG CAGACAAGGTATAGGGCGGCGCCTACAATCCATGCCAACCCGTTCCATGTGCTCGCCGAGGCGG CATAAATCGCCGTGACGATCAGCGGTCCAGTGATCGAAGTTAGGCTGGTAAGAGCCGCGAGCGA TCCTTGAAGCTGTCCCTGATGGTCGTCATCTACCTGCCTGGACAGCATGGCCTGCAACGCGGGC ATCCCGATGCCGCCGGAAGCGAGAAGAATCATAATGGGGAAGGCCATCCAGCCTCGCGTCGCGA ACGCCAGCAAGACGTAGCCCAGCGCGTCGGCCGCCATGCCGGCGATAATGGCCTGCTTCTCGCC GAAACGTTTGGTGGCGGGACCAGTGACGAAGGCTTGAGCGAGGGCGTGCAAGATTCCGAATACC GCAAGCGACAGGCCGATCATCGTCGCGCTCCAGCGAAAGCGGTCCTCGCCGAAAATGACCCAGA GCGCTGCCGGCACCTGTCCTACGAGTTGCATGATAAAGAAGACAGTCATAAGTGCGGCGACGAT AGTCATGCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGAAGGCTCTCAAGGGCATCGGTCGA GATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCGTTGCGCTCACTGCCCGCTTTCC AGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTT GCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCAAGAGCTGATTGCGCTT CACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCCCCAGCAGGCGAAAA TCGTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGTATCGTCGTATCCCA CTACCGAGATATCCGCACCAACGCGCAGGCCGGACTCGGTAATGGCGCGCATTGCGCCCAGCGC CATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGCATGGTT TGTTGAAAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGC GAGTGAGATATTTATGCCAGCCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGGGCCCGC TAACAGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTACCGTCT TCATGGGAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCGGAA CATTAGTGCAGGCAGCTTCCACAGCAATGGCATCCTGGTCATCCAGCGGATAGTTAATGATCAG CCCACTGACGCGTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGT TCTACCATCGACACCACCACGCTGGCACCCAGTTGATCGGCGCGAGATTTAATCGCCGCGACAA TTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCAACGCCAATCAGCAACGACTGTTTGCC CGCCAGTTGTTGTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCACTTTT TCCCGCGTTTTCGCAGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGA CACCGGCATACTCTGCGACATCGTATAACGTTACTGGTTTCACATTCACCACCCTGAATTGACT CTCTTCCGGGCGCTATCATGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATC TCGACGCTCTCCCTTATGCGACTCCTGCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTG AGCACCGCCGCCGCAAGGAATGGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCACGG GGCCTGCCACCATACCCACGCCGAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTC CCCATCGGTGATGTCGGCGATATAGGCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCC ACGATGCGTCCGGCGTAGACGATCGAGATCTCGATCCCGCGAAATTAATACGACTCACTATAGG GGAATTGTGAGCGGATAACAATTCCCCTCTAGAAATAATTTTGTTTAACTTTAAGAAGGAGATA TACCATGGGCCATCATCATCATCATCATCATCATCATCACAGCAGCGGCCATATCGAAGGTCGT CATATG ATGGAGGAGACTGAGCTGATCCAGAGGGCCAAGCTGGCCGAGCAGGCCGGGCGCTACG ACGACATGGCCACCTGCATGAAGGCAGTGACCGAGCAGGGCGCCGAGCTGTCCAACGAGGAGCG CAACCTGCTCTCCGTGGCCTACAAGAACGTGGTCGGGGGCCGCAGGTCCGCCTGGAGGGTCATC TCTAGCATCGAGCAGAAGACCGACACCTCCGACAAGAAGTTGCGGCTGATTAAGGACTATCGGG AGAAAGTGGAGTCCGAGCTGAGATCCATCTGCACCACGGTGCTGGAATTGTTGGATAAATATTT AATAGCCAATGCAACTAATCCAGAGAGTAAGGTCTTCTATCTGAAAATGAAGGGTGATTACTTC CGGTACCTTGCTGAAGTTGCGTGTGGTGATGATCGAAAACAAACGATAGATAATTCCCAAGGAG CTTACCAAGAGGCATTTGATATAAGCAAGAAAGAGATGCAACCCACACACCCAATCCGCCTGGG GCTTGCTCTTAACTTTTCTGTATTTTACTATGAGATTCTTAATAACCCAGAGCTTGCCTGCACG CTGGCTAAAACGGCTTTTGATGAGGCCATTGCTGAACTTGATACACTGAATGAAGACTCATACA AAGACAGCACCCTCATCATGCAGTTGCTTAGAGACAACCTAACACTTTGGACATCAGACAGTGC AGGAGAAGAATGTGATGCGGCAGAAGGGGCTGAAAACCCGAATTCTGGCTCGAGCGGTGGTGGC GGGAGCGGAGGTGGAGGGTCGTCAGGTGTGACCGGCTGCCGGCTGTTCGAGGAGATTCTGTAA G GATCCGGCTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAAC TAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTAT ATCCGGATATCCCGCAAGAGGCCCGGCAGTACCGGCATAACCAAGCCTATGCCTACAGCATCCA GGGTGACGGTGCCGAGGATGACGATGAGCGCATTGTTAGATTTCATACACGGTGCCTGACTGCG TTAGCAATTTAACTGTGATAAACTACCGCATTAAAGCTTATCGATGATAAGCTGTCAAACATGA GAA SEQ ID NO: 63. YAP-TEAD NanoBiT biosensor construct 1: LgBiT- YAP50-171-Flag in pcDNA3.1-hygro vector (6,297 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCGTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGTCTTCACACTCGAAGATTTCGT TGGGGACTGGGAACAGACAGCCGCCTACAACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCC AGTTTGCTGCAGAATCTCGCCGTGTCCGTAACTCCGATCCAAAGGATTGTCCGGAGCGGTGAAA ATGCCCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGCCGACCAAATGGC CCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTG CCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGCTGAACTATTTCGGACGGCCGT ATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAA CAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCTCCATGCTGTTCCGAGTAACCATCAAC AGTGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGGGGOTCGAGCGGTGCCGGGCATCAGATCG TGCACGTCCGCGGGGACTCGGAGACCGACCTGGAGGCGCTCTTCAACGCCGTCATGAACCCCAA GACGGCCAACGTGCCCCAGACCGTGCCCATGAGGCTCCGGAAGCTGCCCGACTCCTTCTTCAAG CCGCCGGAGCCCAAATCCCACTCCCGACAGGCCAGTACTGATGCAGGCACTGCAGGAGCCCTGA CTCCACAGCATGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGTTGGGAGCTGTTTCTCCTGG GACACTGACCCCCACTGGAGTAGTCTCTGGCCCAGCAGCTACACCCACAGCTCAGCATCTTCGA CAGTCTTCTTTTGAGATACCTGATGATGTACTTGTCGTCATCGTCTTTGTAGTC GCGGCCGCTC GAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCAT CTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTC CTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGG GTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGG GCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGCGCCCTG TAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGC GCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCC GTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCC CAAAAAAGTTGATTAGGGTGATGGTTGACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTGGC CCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCA ACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAA AAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAGTTAGGGT GTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGC AACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAAT TAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCG CCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGC CTGTGAGCTATTCGAGAAGTAGTGAGGAGGCTTTTTTGGAGGCGTAGGCTTTTGCAAAAAGCTC GCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGA TTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGA CTGGGCACAACAGACAATCGGCTGGTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGC CCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGGCCTGAATGAACTGCAGGACGAGGCAGCGC GGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGC GGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCT CCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTA CCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGG TCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCC AGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCGATGGCGATGCCTGCTTGC CGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGC GGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGG GCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATC GCCTTCTTGACGAGTTCTTCTGAGGGGGACTCTGGGGTTGGAAATGACCGACCAAGCGACGCCC AACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAaAGGTTGGGCTTCGGAATCG TTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCA CCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACA AATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCGAAACTCATCAATGTATCTTATC ATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGT GTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCC TGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGT CGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCG TATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGA GCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAA AGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTT TTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGA AACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTG TTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTC TCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTG CACGAACCCCCCGTTCAGCCGGACCGGTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTA TGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTA TTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCG GCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAA AGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCA CGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAA AATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTT AATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCC GTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGC GAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCG CAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGA GTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGT CACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATG ATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAG TTGGCGGCAGTGTTATCACTGATGGTTATGGGAGCACTGCATAATTCTCTTACTGTCATGCGAT CCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCG GCGACCGAGTTGCTCTTGGCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTA AAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGA GATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAG CGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATT TCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 64. YAP-TEAD NanoBiT biosensor construct 2: Flag- YAP50-171-LgBiT in pcDNA3.1-hygro vector (6,270 nucieotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGGTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC GCCGGGCATCGGATCGTGCACGTCCG CGGGGACTCGGAGACCGACCTGGAGGCGCTCTTCAACGCCGTCATGAACCCCAAGACGGCCAAC GTGCCCCAGACCGTGCCCATGAGGCTCCGGAAGCTGCCCGACTCCTTCTTCAAGCCGCCGGAGC CCAAATCCCACTCCCGACAGGCCAGTACTGATGCAGGCACTGCAGGAGCCCTGACTCCACAGCA TGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGTTGGGAGCTGTTTCTCCTGGGACACTGACC CCCACTGGAGTAGTCTCTGGCCCAGCAGCTACACCCACAGCTCAGCATCTTCGACAGTCTTCTT TTGAGATACCTGATGATGTAGGCTCGAGCGGTGGTGGCGGGAGCGGAGGTGGAGGGTCGTCAGG TGTCTTCACACTCGAAGATTTCGTTGGGGACTGGGAACAGACAGCCGCCTACAACCTGGACCAA GTCCTTGAACAGGGAGGTGTGTCCAGTTTGCTGCAGAGTCTCGCCGTGTCCGTAGCTCCGATCC AAAGGATTGTCCGGAGCGGTGAAAATGCCCTGAAGATCGACATCCATGTCATCATCCCGTATGA AGGTCTGAGCGCCGACCAAATGGCCCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGGAT GATCATCACTTTAAGGTGATCCTGCCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAACA TGCTGAACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGT AACAGGGACCCTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCTCC ATGCTGTTCCGAGTAACCATCAACAGC GCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGC TGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTT CCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCA TTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGAT TGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAA CCAGCTGGGGCTCTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTC TTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTT TAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTC ACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTT AATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATT TATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAA CGCGAATTAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAG GCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTC CCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTA ACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAA TTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGG AGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGA TCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTT CTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTC TGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTG TCCGGTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCG TTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGA AGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCGGAGAAAGTATCCATCATGGCT GATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTGGACCACCAAGCGAAAC ATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGA AGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGC GAGGATCTCGTCGTGACCGATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCT TTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGC TACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGT ATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGG GACTCTGGGGTTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCC ACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCC TCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAA TGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCT AGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATGATGTCTGTATACCGTCGACCTCTAGCT AGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCC ACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTC ACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGGTGCATT AATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCT CACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTA ATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAA AGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGA GCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAG GCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACC TGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGGTTTGTGATAGCTCACGCTGTAGGTATCTCAG TTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGC TGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGG CAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAA GTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCA GTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTT TTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTT TTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTA TCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTA TATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGAT CTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAG GGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATT TATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGC CTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTG CGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCAT TCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGT TAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTT ATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTG AGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTC AATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCT TCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTG CACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAG GCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTT TTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTA TTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 65. YAP-TEAD NanoBiT biosensor construct 3: SmBiT- YAP50-171-Flag in pcDNA3.1-hygro vector (5,856 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGGCGGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGCACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATGGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCAGTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGTGACCGGCTACCGGCTGTTCGA GGAGATTCTCGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTGCCGGGCAT CAGATCGTGCACGTCCGCGGGGACTCGGAGACCGACCTGGAGGCGCTCTTCAACGCCGTCATGA ACCCCAAGACGGCCAACGTGCCCCAGACCGTGCCCATGAGGCTCCGGAAGCTGCCCGACTCCTT CTTCAAGCCGCCGGAGCCCAAATCCCACTCCCGACAGGCCAGTACTGATGCGGGCGCTGCGGGA GCCCTGACTCCACAGCATGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGTTGGGAGCTGTTT CTCCTGGGACACTGACCCCCACTGGAGTAGTCTCTGGCCCAGCAGCTACACCCACAGCTCAGCA TCTTCGACAGTCTTCTTTTGAGATACCTGATGATGTACTTGTCGTCATCGTCTTTGTAGTC GCG GCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGC CAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCGTTGACCCTGGAAGGTGCCACTCCCACTG TCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGG GGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGAT GCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACG CGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACT TGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGC TTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCGGATTTAGTGCTTTACGGCACC TCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGT TTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACA ACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATT GGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAG TTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGGAGAAGTATGCAAAGCATGCATCTCAATT AGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCA TCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCC AGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCG CCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAA AAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTT CGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCG GCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCA GGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAGGACGAG GCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCA CTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCA CCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGAT CCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGG AAGCCGGTCTTGTCGATCAGGATGATCTGGACCAAGAGCATCAGGGGCTCGCGCCAGCCGAACT GTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCC TGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGG GTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGG CGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCC TTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGC GACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTC GGAATCGTTTTCGGGGACGCGGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCT TCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAA TTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTA TCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGT TTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTG TAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCT TTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCG GTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCT GCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAAC GCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGC TGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAG GTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGC TCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGG CGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGG CTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAG TCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAG CGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAG AACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCT TGATCCGGCAAAGAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCA GAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGA AAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTA AATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACC AATGCTTAATCACTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTG ACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATG ATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGG CCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGA AGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATC GTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAG TTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAG AAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTC ATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGT GTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAG AACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCG CTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTT TCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGC GACACGGAAATGTTGAATACTGATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGT TATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGC GCACATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 66. YAP-TEAD NanoBiT biosensor construct 4: Flag- YAP50-171-SmBiT in pcDNA3.1-hygro vector (5,829 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTGATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGGCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCGAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC GCCGGGCATCAGATCGTGCACGTCCG CGGGGACTCGGAGACCGACCTGGAGGCGCTCTTCAACGCCGTCATGAACCCCAAGACGGCCAAC GTGCCCCAGACCGTGCCCATGAGGCTCCGGAAGCTGCCCGACTCCTTCTTCAAGCCGCCGGAGC CCAAATCCCACTCCCGACAGGCCAGTACTGATGCAGGCACTGCAGGAGCCCTGACTCCACAGCA TGTTCGAGCTCATTCCTCTCCAGCTTCTCTGCAGTTGGGAGCTGTTTCTCCTGGGACACTGACC CCCACTGGAGTAGTCTCTGGCCCAGCAGCTACACCCACAGCTCAGCGTCTTCGACAGTCTTCTT TTGAGGTACCTGATGATGTAGGCTCGAGCGGTGGTGGCGGGAGCGGAGGTGGAGGGTCGTCAGG TGTGACCGGCTACCGGCTGTTCGAGGAGATTCTG GCGGCCGCTCGAGTCTAGAGGGCCCGTTTA AACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCC GTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTG CATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGG GGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGGG GAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCATTAAGCGCGG CGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCGTTT CGCTTTCTTCCCTTCCTTTCTCGCCACGTTGGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGG GTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTG ATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCAC GTTCTTTAATAGTGGAGTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCT TTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAA AATTTAACGGGAATTAATTCTGTGGAATGTGTGTGAGTTAGGGTGTGGAAAGTCCCCAGGCTCC CCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCCC CAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCC GCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGC TGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGT AGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCAT TTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGGAC GCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGAC CGACCTGTCCGGTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACG ACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTAT TGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCAT CATGGCTGATGCAATGGGGGGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCAGCAA GCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATC TGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCC CGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAAT GGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAG CGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCT TTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTC TGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTT CGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGG ATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAG CTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACT GCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGACC TCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCA CAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAG CTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAG CTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTT CCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAA GGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGC CAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCC CTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAG ATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACC GGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGT ATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCC CGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCG CCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGT TCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCT GAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGT AGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTT TGATCTTTTCTACGGGGTGTGAGGCTCAGTGGAAGGAAAACTCACGTTAAGGGATTTTGGTCAT GAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATC TAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCT CAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGAT ACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCT CCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTT TATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAA TAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATG GCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAA AAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCAGT CATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTG ACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCC CGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAA ACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCC ACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAA CAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACT CTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATAGATATTT GAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTG ACGTC SEQ ID NO: 67. YAP-TEAD NanoBiT biosensor construct 5: LgBiT- TEAD1-194-411-Myc in pcDNA3.1-hygro vector (6,592 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGAGAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGGCCAGTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGTCTTCACACTCGAAGGTTTCGT TCGGGACTGGGAACAGACAGCCGCCTACAACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCC AGTTTGCTGCAGAATCTCGCCGTGTCCGTAACTCCGATCCAAAGGATTGTCCGGAGCGGTGAAA ATGCCCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGCCGACCAAATGGC CCAGATCGAAGAGGTGTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTG CCCTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGCTGAACTATTTCGGACGGCCGT ATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAA CAAAATTATCGACGAGCGCCTGATCACCCCCGACGGCTCCATGCTGTTCCGAGTAACCATCAAC AGTGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTTGAGCCTGCATCGGCC CCAGCTCCCTCAGTCCCTGCCTGGCAAGGTCGCTCCATTGGCACGACCGAGCTTCGCCTGGTGG AATTTTCAGCTTTTCTCGAGCAGCAGCGAGACCCAGACTCGTACAACAAACACCTCTTCGTGCA CATTGGGCATGCCGACCGTTCTTACAGTGACCCATTGCTTGAATCAGTGGGCATTCGTCAGATT TATGACAAATTTCCTGAAAAGAAGGGTGGCTTAAAGGAACTGTTTGGAAAGGGCCCTCAAGATG CCTTCTTCCTCGTA A AATTCTGGGCTGATTTAAACTGCAATATTCAAGATGATGCTGGGGCTTT TTATGGTGTAACCAGTCAGTACGAGAGTTCTGAAAATATGACAGTCACCTGTTCCACCAAAGTT TGCTCCTTTGGGGAGCAAGTGGTAGAGAAAGTAGAGACGGAGTATGCAAGGTTTGAGGATGGCC GATTTGTATACCGAATAAACCGCTCCCCAATGTGTGAATATATGATCAACTTCATCCACAAGCT CAAACACTTACCAGAGAAATATATGATGAACAGTGTTTTGGAAAACTTCACAATTTTATTGGTG GTAACAAACAGGGATACACAAGAAACTCTACTCTGCATGGCCTGTGTGTTTGAAGTTTCAAATC AGATCCTCTTCTGAGATGAGTTTTTGTTC GCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCC GCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCGCCGTGCC TTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCG CATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGG ATTGGGAAGACAATAGCAGGGATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAG AACCAGCTGGGGCTCTAGGGGGTATCCCGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTT TCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCC TTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGT TCACGTAGTGGGCCATCGGCCTGATAGAGGGTTTTTCGCCCTTTGAGGTTGGAGTCCACGTTGT TTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTGGGTGTATTCTTTTGA TTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAAGAAAAATTT AACGCGAATTAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGC AGGCAGAAGTATGCAAAGCATGCATCTGAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGC TCCCGAGCAGGCAGAAGTATGCAAAGCATGCATGTCAATTAGTCAGCAACGATAGTCCCGCCCC TAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACT AATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGA GGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCG GATCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGG TTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGC TCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACC TGTCCGGTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGG CGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGC GAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGG CTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAA ACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGAC GAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACG GCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCG CTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTG GCTACCCGTGATATTGCTGAAGAGCTTGGCCGCGAATGGGCTGACCGCTTCCTCGTGCTTTACG GTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGC GGGACTCTGGGGTTCGAAATGACCGACCAAGCGACGCCGAACCTGCCATCACGAGATTTCGATT CCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGAT CCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTAT AATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATT CTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGACCTCTAG CTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATT CCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAAC TCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCA TTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCG CTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGG TAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCA AAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGAC GAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACC AGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATA CCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTC AGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACC GCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACT GGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGGGGTGCTACAGAGTTCTTG AAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGC CAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGG TTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATC TTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGAT TATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAG TATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATGTCAGCG ATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGG AGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGA TTTATCAGCAATAAACCAGCCAGCCGGAAGGGCGGAGCGCAGAAGTGGTCCTGCAACTTTATCC GCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTT TGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTC ATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCG GTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGG TTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGG TGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCG TCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTT CTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCG TGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGA AGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCC TTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATG TATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 68. YAP-TEAD NanoBiT biosensor construct 6: Myc- TEAD1-194-411-LgBiT in pcDNA3.1-hygro vector (6,559 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCACTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC TGAGCCTGCATCGGCGCCAGCTCCCT CAGTCCCTGCCTGGCAAGGTCGCTCCATTGGCACAACCAAGCTTCGCCTGGTGGAATTTTCGGC TTTTCTCGAGC A GCAGCGAGACCCAGACTCGTACAACAAACACCTCTTCGTGCACGTTGGGCAT GCCAACCATTCTTACAGTGACCCATTGCTTGAATCAGTGGACATTCGTCAGATTTATGACAAAT TTCCTGAAAAGAAAGGTGGCTTAAAGGAACTGTTTGGAAAGGGCCCTCAAAATGCCTTCTTCCT CGTAAAATTCTGGGCTGATTTAAACTGCAATATTCAAGATGATGCTGGGGCTTTTTATGGTGTA ACCAGTCAGTACGAGAGTTCTGAAAATATGACAGTCACCTGTTCCACCAAAGTTTGCTCCTTTG GGAAGCAAGTAGTAGAAAAAGTAGAGACGGAGTATGCAAGGTTTGAGAGTGGCCGATTTGTATA CCGAATAAACCGCTCCCCAATGTGTGAATATATGATCAACTTCATCCACAAGCTCAAACACTTA CCAGAGAAATATATGATGAACAGTGTTTTGGAAAACTTCACAATTTTATTGGTGGTAACA A ACA GGGATACACAAGAAACTCTACTCTGCATGGCCTGTGTGTTTGAAGTTTCAAATGGCTCGAGCGG TGGTGGCGGGAGCGGAGGTGGAGGGTCGTCAGGTGTCTTCACACTCGAAGATTTCGTTGGGGAC TGGGAACAGACAGCCGCCTACAACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGC TGCAGAATCTCGCCGTGTCCGTAACTCCGATCCAAAGGATTGTCCGGAGCGGTGAAAATGCCCT GAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGCCGACCAAATGGCCCAGATC GAAGAGGTGTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTGCCCTATG GCACACTGGTAATCGACGGGGTTACGCCGAACATGCTGAACTATTTCGGACGGCCGTATGAAGG CATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAACAAAATT ATCGACGAGCGCCTGATCACCCCCGACGGCTCCATGCTGTTCCGAGTAACCATCAACAGC GCGG CCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCC AGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCGACTGT CCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGG GGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATG CGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGC GCGCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGGTACACTT GCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCGCTTCCTTTCTCGCCACGTTCGCCGGCT TTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCT CGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTT TTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAA CACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTG GTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAGT TAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATCCATCTCAATTA GTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCAT CTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCA GTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGC CTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAA AAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTC GCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGG CTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAG GGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAGGACGAGG CAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCAC TGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCAC CTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATC CGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGA AGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTG TTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCT GCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGG TGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGC GAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCT TCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGCG ACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCG GAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTT CGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAAT TTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTAT CTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTT TCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGT AAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT TCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGG TTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTG CGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACG CAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCT GGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGG TGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCT CTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGC GCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGC TGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGT CCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGC GAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGA ACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTAGCTTCGGAAAAAGAGTTGGTAGCTCTT GATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAG AAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAA AACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAA ATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCA ATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGA CTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGA TACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGC CGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAA GCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCG TGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGT TACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGA AGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCA TGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTG TATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGC TGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTT CACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCG ACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTT ATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCG CACATTTCCCCGAAAAGTGCCACCTGACGTC SEQ ID NO: 69. YAP-TEAD NanoBiT biosensor construct 7: SmBiT- TEAD1-194-411-Myc in pcDNA3.1-hygro vector (6,151 nucieotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTGATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTGCCATAGTAACGCCAATAGGGACTTTCCATTGACGTGAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGGGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGAGTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC ATGGTGACCGGCTACCGGGTGTTCGA GGAGATTCTCGGGAGTTCCGGTGGTGGCGGGAGCGGAGGTGGAGGCTCGAGCGGTTGAGCCTGC ATCGGCCCCAGCTCCCTCAGTCCCTGCCTGGCAAGGTCGCTCCATTGGCACAACCAAGCTTCGC CTGGTGGAATTTTCAGCTTTTCTCGAGCAGCAGCGAGACCCAGACTCGTACAACAAACACCTCT TCGTGCACATTGGGCATGCCAACCATTCTTACAGTGACCCATTGCTTGAATCAGTGGACATTCG TCAGATTTATGACAAATTTCCTGAAAAGAAAGGTGGCTTAAAGGAACTGTTTGGAAAGGGCCCT CAAAATGCCTTCTTCCTCGTAAAATTCTGGGCTGATTTAAACTGCAATATTCAAGATGATGCTG GGGCTTTTTATGGTGTAACCAGTCAGTACGAGAGTTCTGAAAATATGACAGTCACCTGTTCCAC CAAAGTTTGCTCCTTTGGGAAGCAAGTAGTAGAAA A AGTAGAGACGGAGTATGCAAGGTTTGAG AGTGGCCGATTTGTATACCGAATAAACCGCTCCCCAATGTGTGAATATATGATCAACTTCATCC ACAAGCTCAAACACTTACCAGAGAAGTATATGATGAACAGTGTTTTGGAAAACTTCACAATTTT ATTGGTGGTAACAAACAGGGATACACAAGAAACTCTACTCTGCATGGCCTGTGTGTTTGAAGTT TCAAATCAGATCCTCTTCTGAGATGAGTTTTTGTTC GCGGCCGCTCGAGTCTAGAGGGCCCGTT TAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCGAGCCATCTGTTGTTTGCCCCTCCC CCGTGCCTTCCTTGACCCTGGAAGGTGCGACTCCCACTGTCCTTTCCTAATAAAATGAGGAAAT TGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAG GGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGG CGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCACGCGCCCTGTAGCGGCGCATTAAGCGC GGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCT TTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGG GGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGG TGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCC ACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATT CTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACA AAAATTTAACGCGAATTAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCCAGGCT CCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTC CCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTC CCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATG GCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAA GTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCC ATTTTCGGATCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGC ACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAAT CGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGGAGGGGCGCCCGGTTCTTTTTGTCAAG ACCGACCTGTCCGGTGCCCTGAATGAACTGGAGGACGAGGCAGCGCGGCTATCGTGGCTGGCGA CGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCT ATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCC ATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACC AAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGA TCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATG CCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAA ATGGCCGCTTTTCTGGATTCATCGACTGTGGCGGGCTGGGTGTGGCGGACCGCTATCAGGACAT AGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTG CTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCT TCTGAGCGGGACTCTGGGGTTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGAT TTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCT GGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGC AGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCA CTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGA CCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCT CACAATTCCAGACAACATAGGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTG AGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGGTTTCCAGTCGGGAAACCTGTCGTGCC AGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGC TTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCA AAGGCGGTAATAGGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAG GCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCC CCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAA AGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTA CCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAG GTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAG CCCGACCGCTGCGCGTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTAT CGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGA GTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTG CTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCAGCGCTG GTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCC TTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTGACGTTAAGGGATTTTGGTC ATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAA TGTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACGTAT CTCAGCGATCTGTGTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACG ATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGG CTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAAC TTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGGCAGTT AATAGTTTGCGCAACGTTGTTGCCATTGGTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTA TGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAA AAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATGA CTCATGGTTATGGCAGCACTGCATAATTGTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTG TGACTGGTGAGTACTCAACGAAGTCATTCTGAGAATAGTGTATGCGGCGAGCGAGTTGGTCTTG CCCGGGGTCAATAGGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGA AAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAAC CCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAA AACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATA CTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATAT TTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACC TGACGTC SEQ ID NO: 70. YAP-TEAD NanoBiT biosensor construct 8: Myc- TEAD1-194-411-SmBiT in pcDNA3.1-hygro vector (6,118 nucleotides) GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGC ATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGC GTTTTGCGCTGCTTCGCGATGTAGGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTA TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAA CTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGA CGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACG GTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTC AATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTGAATGGG AGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAG AGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC TGAGCCTGCATCGGCCCCAGCTCCCT CAGTCCCTGCCTGGCAAGGTCGCTCCATTGGCACAACCAAGCTTCGCCTGGTGGAATTTTCAGC TTTTCTCGAGCGGCAGCGAGACCCAGACTCGTACAACAAACACCTCTTCGTGCACATTGGGCAT GCCAACCATTCTTACAGTGACCCATTGCTTGAATCAGTGGACATTCGTCAGATTTATGACAAAT TTCCTGAAAAGAAAGGTGGCTTAAAGGAACTGTTTGGAAAGGGCCCTCAAAATGCCTTCTTCCT CGTAAAATTCTGGGCTGATTTAAGCTGCAATATTCAAGATGATGCTGGGGCTTTTTGTGGTGTA ACCAGTCAGTACGAGAGTTCTGAAAATATGACAGTCACCTGTTCCACCAAAGTTTGCTCCTTTG GGAAGCAGGTAGTAGAAGAAGTAGAGACGGAGTATGCAAGGTTTGAGAATGGCCGATTTGTATA CCGAATAAACCGCTCCCCAATGTGTGAATATATGATCAACTTCATCCACAAGCTCAAACACTTA CCAGAGAAATATATGATGAACAGTGTTTTGGAAAACTTCACAATTTTATTGGTGGTAACAAACA GGGATACACAAGAAACTCTACTCTGCATGGCCTGTGTGTTTGAAGTTTCAAATGGCTCGAGCGG TGGTGGCGGGAGCGGAGGTGGAGGGTCGTCAGGTGTGACCGGCTACCGGCTGTTCGAGGAGATT CTG GCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTGGACTGTGCCTTCT AGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTC CCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATGGCATTGTCTGAGTAGGTGTCATTCTAT TCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCT GGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATC CCCACGCGCCGTGTAGCGGGGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGC TACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTC GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTAC GGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATA GACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACT GGAAGAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGG CCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTG TGTCAGTTAGGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATC TCAATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAG CATGCATGTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACT CCGCCCAGTTCCGCCGATTCTCCGGCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCG AGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTT TTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAAGAGACAGGATGAGGA TCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGC TATTCGGCTATGAGTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGGTGTC AGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAG GACGAGGCAGCGCGGGTATCGTGGCTGGCCACGACGGGCGTTCCTTGGGCAGCTGTGCTCGACG TTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTC ATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGGGGGTGCATACG CTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTC GGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGC CGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGC GATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCC GGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCT TGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGC ATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGAAATGACCGA CCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTG GGCTTCGGAATCGTTTTCCGGGACGCGGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGG AGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCAT CACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATC AATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCAT AGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCAT AAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTG CCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGA GAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGT TCGGCTGCGCCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGG GATAACGGAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCG CGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAG TCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTC GTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAA GCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAA GCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGT CTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTA GCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACAC TAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGT AGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTA CGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTG GAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTG CTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACA GTTAGCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGT TGCCTGACTCCCCGTCGTGTAGATAAGTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCT GCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCG GAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTG CCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACA GGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAA GGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTT ACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAG AATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACA TAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATC TTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTT TTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAAT AAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTAT CAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGG TTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC

EQUIVALENTS

While the invention has been described with respect to illustrative embodiments thereof, it will be understood that various changes may be made to the embodiments without departing from the scope of the invention. Accordingly, the described embodiments are to be considered merely exemplary and the invention is not to be limited thereby.

REFERENCES

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The invention claimed is:
 1. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of firefly luciferase fused to at least one fragment of YAP.
 2. The DNA construct of claim 1, wherein the fragment of firefly luciferase comprises amino acids 1-416 of SEQ ID NO:6 and is N-terminal to the at least one fragment of YAP comprising amino acids 120-134 of SEQ ID NO:2.
 3. The DNA construct of claim 1, wherein the fragment of firefly luciferase comprises amino acids 1-544 of SEQ ID NO:6 and is N-terminal to the at least one fragment of YAP comprising amino acids 120-134 of SEQ ID NO:2.
 4. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of firefly luciferase fused to at least one fragment of 14-3-3 protein, wherein the at least one fragment of 14-3-3 protein is capable of binding to YAP.
 5. The DNA construct of claim 4, wherein the at least one fragment of 14-3-3 protein comprises SEQ ID NO:4 and is N-terminal to the fragment of firefly luciferase comprising amino acids 394-550 of SEQ ID NO:6.
 6. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of NanoBiT luciferase fused to at least one fragment of YAP.
 7. The DNA construct of claim 6, wherein the fragment of NanoBit luciferase is LgBiT comprising amino acid sequence SEQ ID NO:52 and is N-terminal to the at least one fragment of YAP comprising amino acids 120-134 of SEQ ID NO:2.
 8. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of NanoBiT luciferase fused to at least one fragment of 14-3-3 protein, wherein the at least one fragment of 14-3-3 protein is capable of binding to YAP.
 9. The DNA construct of claim 8, wherein the at least one fragment of 14-3-3 protein comprises SEQ ID NO:4 and is N-terminal to the fragment of NanoBit luciferase that is SmBiT comprising amino acid sequence SEQ ID NO:54.
 10. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of NanoBit luciferase that is LgBiT comprising amino acid sequence SEQ ID NO:52 and a fragment of YAP comprising amino acids 50-171 of SEQ ID NO:2.
 11. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of NanoBit luciferase that is SmBiT comprising amino acid sequence SEQ ID NO:54 and a fragment of YAP comprising amino acids 50-171 of SEQ ID NO:2.
 12. A DNA construct comprising a nucleic acid sequence encoding a fusion protein comprising a fragment of NanoBiT luciferase fused to at least one fragment of TEAD protein, wherein the at least one fragment of TEAD protein is capable of binding to YAP.
 13. The DNA construct of claim 12, wherein the fragment of NanoBit luciferase is LgBiT comprising amino acid sequence SEQ ID NO:52 and the at least one fragment of TEAD protein comprises amino acids 194-411 of SEQ ID NO:50.
 14. The DNA construct of claim 12, wherein the fragment of NanoBit luciferase is SmBiT comprising amino acid sequence SEQ ID NO:54 and the at least one fragment of TEAD protein comprises amino acids 194-411 of SEQ ID NO:50. 